Surgery Hemostasis, Surgical Bleeding, and Transfusion
DR. Bibera July 5, 2012
BIOLOGY OF HOMEOSTASIS
a complex process whose function is to limit blood loss from an injured vessel 4 major physiologic events o vascular constriction o platelet plug formation o fibrin formation o fibrinolysis
Vascular Constriction is the initial response to vessel injury, more pronounced in vessels with medial smooth muscles dependent on local contraction of smooth muscle subsequently linked to platelet plug formation potent vasoconstrictors: vasoconstrictors: A2 (TXA2) is produced locally at o Thromboxane A2 the site of injury via the release of arachidonic acid from platelet membranes o Endothelinsynthesized Endothelinsynthesized by injured endothelium and serotonin (5-hydroxytryptamine) released during platelet aggregation Bradykinin and Fibrinopeptides o Bradykinin and the extent of vasoconstriction varies with the degree of vessel injury Platelet Function platelets are anucleate fragments of megakaryocytes, normal circulating number of platelets ranges between 150,000 and 400,000/ L up to 30% may be sequestered in the spleen if not consumed in a clotting reaction, platelets are normally removed by the spleen and have an average life span of 7 to 10 days 10 days platelets play an integral role in hemostasis by forming a hemostatic plug and by contributing to thrombin formation injury to the intimal layer in the vascular wall exposes subendothelial collagen to which platelets adhere, which requires von Willebrand's factor (vWF) binds to glycoprotein I/IX/V on the platelet membrane
NAMES NG TRANS PEOPLE
1-4
after adhesion, platelets initiate a release reaction that recruits other platelets from the circulating blood to seal the disrupted vessel. Up to this point, this process is known as primary hemostasis platelet aggregation is reversible and is not associated with secretion o heparin does not interfere with this reaction (ADP)) and serotonin serotonin are o adenosine diphosphate (ADP the principal mediators in platelet aggregation
arachidonic acid released converted by COX to prostaglandin G2 (PGG2) prostaglandin H2 (PGH2) converted to TXA2 effects:Arachidonic acid shuttled to adjacent endothelial cells converted to prostacyclin (PGI2 ) vasodilation and acts to inhibit platelet aggregation
platelet COX is o irreversibly inhibited by aspirin o reversibly blocked by NSAIDs o but is not affected by COX-2 inhibitor
in the second wave of platelet aggregation, a release reaction occurs in which several substances, including ADP, Ca2+,serotonin, TXA2, and -granule proteins are discharged
fibrinogen is a required cofactor, acting as a bridge for the glycoprotein IIb/IIIa receptor on the activated platelets its release causes compaction of the plateletsinto a plug, a process that is irreversible thrombospondin , secreted by the granule, stabilizes fibrinogen binding to the activated platelet surface and strengthens the platelet-platelet interactions. platelet factor 4 4 (PF4), potent heparin antagonist, and thromboglobulin also are secreted during the release reaction
the second wave of platelet aggregation is inhibited by aspirin and NSAIDs, by (cAMP), and by nit ric oxide
alterations occur in the phospholipids of the platelet membrane that allow Ca2+ and clotting factors bind to the platelet surface enzymatically active complexes
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o
the altered lipoprotein surface (sometimes referred to as platelet factor 3) catalyzes reactions that are involved in:
activation than is extrinsic (tissue factor-VIIa) complex, five to six orders of magnitude more effective than is factor IXa alone
- conversion of prothrombin to thrombin by
o
activated factor X (Xa) in the presence of factor V and Ca2+ - is also involved in the reaction by which activated factor IX (IXa), factor VIII, and Ca2+ activate factor X
o
Coagulation o
the coagulation cascade has 2 intersecting pathways: o Intrinsic pathway - begins with factor XII and through a cascade of reactions activates factors XI, IX, and VII in sequence fibrin clot formation, intrinsic to the circulating plasma and no surface is required to initiate the process o Extrinsic pathway - requires exposure of tissue factor on the surface of the injured vessel wall to initiate the cascade beginning with factor VII
o
the prothrombinase is significantly more effective at catalyzing its substrate than is factor Xa alone once formed, thrombin leaves the membrane surface converts fibrinogen by two cleavage steps into fibrin and 2 small peptides termed fibrinopeptides A and B removal of fibrinopeptide A permits end-to-end polymerization of the fibrin cleavage of fibrinopeptide B allows side-to-side polymerization of the fibrin clot, facilitated by thrombin-activatable fibrinolysis inhibitor(TAFI)
the coagulation system is exquisitely regulated. Feedback inhibition on the coagulation cascade deactivates the enzyme complexes leading to thrombin formation
exists at upstream, intermediate, and downstream portions of the coagulation cascade to "turn off" thrombin formation once the procoagulantsequence is initially activated
the two arms of the coagulation cascade merge to a common pathway at factor X activation sequence of factors II (prothrombin) and I (fibrinogen) clot formation occurs after proteolytic conversion of fibrinogen to fibrin an elevated activated partial thromboplastin time(aPTT) abnormal function Intrinsic pathway an elevated prothrombin time (PT) abnormal extrinsic pathway vitamin K deficiency and warfarin use affect factors II, VII, IX, and X fibrinogen levels of <50 mg/dL causes prolongation of the PT and aPTT primary pathway for coagulation is initiated by theexposure of subendothelial tissue factor when vessel surface is injured
Coagulation Factors Tested by the PT and the aPTT PT
aPTT
VII
XII
X
High molecular weight kininogen
V
Prekallikrein
II (prothrombin)
XI
Fibrinogen
IX VIII X V
propagation of the clotting reaction then ensues with a sequence of enzymatic reactions, which involves a proteolytic enzyme cleavage of a proenzyme and a phospholipid surface generates the next enzyme in a cascade manner
II Fibrinogen
o
each reaction requires a helper protein (i.e. Factor VIIa binds to tissue factor, and tissue factor-VIIa complex catalyzes the activation of factor X to factor Xa)
Based on 3 mechanisms: o
o o
o
the reaction takes place on the phospholipid surface of activated platelets this complex is four orders of magnitude more active at converting factor X than is factor VIIa alone and also activates factor IX to factor IXa o
o
o
o
factor Xa, together with factor Va and Ca2+ and phospholipid, comprises the prothrombinase complex that converts prothrombin to thrombin thrombin has multiple functions in the clotting process, including conversion of fibrinogen to fibrin and activation of factors V, VII, VIII, XI,and XIII, as well as activation of platelets factor VIIIa combines with factor IXa to form the intrinsic factor complex (VIIIa-IXa), which is responsible for the bulk of the conversion of factor X to Xa50x more effective at catalyzing factor X
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mechanisms of fibrinolysis allow for breakdown of the fibrin clot and subsequent repair of vessel with deposition of connective tissue tissue factor pathway inhibitor (TFPI) blocks the extrinsic tissue factor–VIIa complex eliminating this production of factors Xa and IXa - Antithrombin III effectively neutralizes all of the procoagulant serine proteases and weakly inhibits the tissue factor–VIIa complex mechanism of inhibition of thrombin formation is the protein C system - thrombin binds to thrombomodulin and activates
protein C to activated protein C (APC), which then forms a complex with its cofactor, protein S, on a phospholipid surface cleaves factors Va and VIIIa no longer able to participate in the formation of tissue factor–VIIa or prothrombinasecomplexe - also activates TAFI, which removes the terminal
lysine on the fibrin molecule clot susceptible to lysis by plasmin
more
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- factor V Leide, gene mutation, that is resistant to
cleavage by APC predisposed thromboembolic events
to
venous
o
be incorporated into the clot in lieu of normal fibrin monomers unstable clot. D-dimers in the circulationmarker of thrombosis or other conditions in which a significant activation of the fibrinolytic system is present
degradation of fibrin clot is accomplished by plasmin, a serine protease derived from the proenzyme plasminogen tissue plasminogen activator (tPA) is made by the endothelium and is the main circulating form of this family of enzymes o is selective for fibrin-bound plasminogen so that endogenous fibrinolytic activity occurs predominately at the site of clot plasminogen activator (uPA), also o urokinase produced by endothelial cells, as well as by urothelium, is not selective for fibrin-bound plasminogen
CONGENITAL FACTOR DEFICIENCIES Most frequent inherited factor deficiencies
factor VIII deficiency (hemophilia Willebrand's disease) factor IX deficiency (hemophilia B disease) factor XI deficiency
A
and
von
or
Christmas
Factor VIII And Factor IX Hemophilia
sex-linked recessive disorders Severity of both hemophilia A and hemophilia B depends on the level of factor VIII or factor IX in the patient's plasma Disease factor levels:
Fibrinolysis fibrin clot undergoes clot lysis, which permits restoration of blood flow fibrinolysis is initiated at the same time as the clotting mechanismunder the influence of circulating kinases, tissue activators, and kallikrein plasmin- main enzyme degrades the fibrin mesh at various places plasminogen may be converted by one of several plasminogen activators, including tPA and uPA bradykinin, a potent endothelium-dependent vasodilator cleaved from high molecular weight kininogen by kallikrein, causes contraction of nonvascular smooth muscle, increases vascular permeability, and enhances release of tPA plasminogen activation may be initiated by activation of factor XII the tPA activates plasminogen more efficiently when it is bound to fibrin, so that plasmin is formed selectively on the clot o plasmin is inhibited by 2-antiplasmin, a protein that is cross-linked to fibrin by factor XIII, which helps to ensure that clot lysis does not occur too quickly circulating plasmin also is inhibited by 2o any antiplasmin and circulating tPA or urokinase clot lysis yields fibrin degradation products, including E-nodules and D-dimers smaller fragments interfere with normal o the platelet aggregation and the larger fragments may
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<1% normal: Severe Disease 1 - 5%: moderately severe disease 5 - 30%: mild disease MANIFESTATIONS:
Intracranial bleeding, retropharyngeal bleeding, and bleeding from the tongue or lingual frenulum may be life-threatening Moderately severe hemophilia: less spontaneous bleeding but are likely to bleed severely after trauma or surgery Retroperitoneal hematomas Mild hemophiliacs: do not bleed spontaneously and have mild bleeding after major trauma or surgery May not bleed immediately after an injury or minor surgery but will begin to bleed several hours later because of normal platelet function
TREATMENT:
Factor VIII (hemo A) or factor IX (hemo B) concentrate Recombinant factor VIII recommended for HIV and hepa C virus (HCV)-seronegative For factor IX replacement :recommended tx are recombinant or high purity factor IX Intermediate purity factor IX (prothrombin complex) concentrates (not use: risk of thrombosis) 1-deamino-D-argininevasopressin (DDAVP, desmopressin): induces the release of vWF from endothelial cells, raising the levels of vWF and associated factor VIII
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Aminocaproic acid (Amicar): inhibitor of fibrinolysis, useful adjunct to factor VIII or IX or DDAVP especially for oral and urinary tract bleeding
Patients with high titer inhibitors is not possible to achieve adequate factor VIII levels with factor VIII preparations
TREATMENT:
Alternatives:
Porcine factor VIII Prothrombin complex concentrates Recombinant factor VIIa (most effective, given every 2 hrs, expensive)
Von Willebrand’s Disease
Disorder with low factor VIII Autosomal dominant disorder Primary defect: low level of the vWF, a large glycoprotein with two functions 1. Serve as a carrier for factor VIII 2. Necessary for normal platelet adhesion and normal aggregation under high shear conditions
Half-life of factor X is approximately 48 hours Factor V deficiency may be coinherited with factor VIII deficiency
FFP. Contains 1 unit of activity of each (factors X and II) per milliliter. However, factor V activity is decreased because of its inherent instability. Half-life of factor II is long (approximately 72 hours) and only 25% of the normal level is needed for hemostasis, single infusion of FFP is sufficient. Prothrombin complex concentrates can be used to treat deficiencies of prothrombin or factor X. Treatment of bleeding in combined deficiency (factor V and factor VIII deficiency) requires factor VIII concentrate and FFP. Some factor V deficient pt also lacks factor V normally present in platelets and may need platelet transfusions as well as FFP
Three types: a) Type I (partial quantitative deficiency) b) Type II (qualitative defect) c) Type III (total deficiency)
Factor VII Deficiency
Rare disorder Bleeding is uncommon unless the level is less than 3%
TREATMENT: MANIFESTATIONS:
Menorrhagia is common in women with vWD Easy bruising and mucosal bleeding (platelet disorder)
FFP or with recombinant factor VIIa Half-life of recombinant factor VIIa is approximately 2 hours Half-life of factor VII in FFP is approximately 4 hours
TREATMENT: Intermediate purity factor VIII concentrates (HumateP: contains vWF and factor VIII) DDAVP: raises endogenous vWF levels by release of the factor from endothelial cells - EACA (Amicar) is a useful adjunct
MANIFESTATIONS:
In general, type I patients respond well to DDAVP, type II patients may respond, depending on the particular defect and type III patients usually do not respond. Factor XI Deficiency
Hemophilia C Prevalent in the Ashkenazi Jewish population (heterozygote frequency about 1:8) Mild bleeding disorder, autosomal recessive trait
Factor XIII Deficiency Rare, autosomal recessive trait
Bleeding is delayed because clots form normally but are susceptible to fibrinolysis Umbilical stump bleeding high risk of intracranial bleeding Spontaneous abortion is usual in women unless they receive replacement therapy Half-life of factor XIII is approximately 9 to 14 days
TREATMENT:
Replacement with FFP, cryoprecipitate, or a factor XIII concentrate Levels of 1 - 2% : adequate for hemostasis
MANIFESTATIONS:
PLATELET FUNCTIONAL DEFECTS
Spontaneous bleeding is rare, but may occur after surgery or trauma
Inherited Defects
TREATMENT:
Fresh-frozen plasma (FFP) infusion Factor XI concentrates DDAVP: useful in prevention of surgical bleeding
Rare defects Abnormalities of platelet surface proteins, platelet granules, and enzyme defects Major surface protein abnormalities are thrombasthenia and Bernard-Soulier syndrome
Deficiencies Of Factors II (Prothrombin), V & X
Rare inherited deficiencies autosomal recessive traits Significant bleeding in homozygotes with <1% of normal activity Half-life of prothrombin (factor II) is approximately 72 hours
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THROMBASTHENIA (GLANZMANN'S DISEASE)
Caused by an absence of functional glycoprotein IIb IIIa, the receptor for fibrinogen and also a receptor for vWF Because platelets must bind fibrinogen or vWF to expose the ADP receptor so they can bind ADP and
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aggregate, platelets of thrombasthenic patients do not aggregate Treatment: platelet transfusions
Etiology of Platelet Disorders A. Quantitative disorders 1.
BERNARD-SOULIER SYNDROME
Caused by a defect in the GP Ib/IX/V receptor for vWF -necessary for platelet adhesion Treatment: Platelet transfusion
STORAGE POOL DISEASE
Most common intrinsic platelet defect May involve loss of dense granules (storage sites for ADP, ATP, Ca2+, and inorganic phosphate) and α granules
2.
Failure of production: related to impairment of bone marrow function a.
Leukemia
b.
Myeloproliferative disorders
c.
Vitamin B12 or Folate deficiency
d.
Chemotherapy or radiation therapy
e.
Acute alcohol intoxication
f.
Viral infections
Decreased survival a.
DENSE GRANULE DEFICIENCY
Most prevalent May be an isolated defect or occur with partial albinism in the Hermansky-Pudlak syndrome Bleeding is variable depending on how severe the granule defect is Bleeding is primarily caused by the decreased release of ADP from these platelets
o
Isolated defect of the α-granules Bleeding is usually mild dense and α-granules: more severe bleeding disorder Treatment: DDAVP platelet transfusion: severe bleeding
Rare Treatment: platelet transfusion, if significant
o o
o
or
b.
Disseminated intravascular coagulation
c.
Disorders related to platelet thrombi o
Thrombocytopenic purpura
o
Hemolytic uremic syndrome
Sequestration a.
Portal hypertension
b.
Sarcoid
c.
Lymphoma
d.
Gaucher's disease
Massive transfusion
2.
Therapeutic administration of platelet inhibitors
3.
Disease states a.
Myeloproliferative disorders
b.
Monoclonal gammopathies
c.
Liver disease
marrow related diseases (leukemia or myelodysplasia, vitamin B12 or folate deficiencies, chemotherapy or radiation therapy, acute alcohol intoxication, or viral illnesses ) affects bone marrow production Shortened platelet thrombocytopenia
survival
in
associated with other autoimmune disorders or lowgrade B-cell malignancies disseminated intravascular coagulation
Secondary immune thrombocytopenia
o
very low platelet count
o
with petechiae and purpura
o
with epistaxis
o
initial treatment
With indicated treatment, due to symptoms or the need for an invasive procedure platelet transfusion is used
Dave.Linelle.Deane.Mhe.Te.Paul
immune
may be idiopathic
Platelet Abnormalities Due to failure of production as in bone marrow disorders (cuased by leukemia, myelodysplastic syndrome, severe vitaminB12 or folate deficiency, chemotherapeutic drug use, radiation therapy, acute ethanol intoxication, or viral infection) Shortened survival Sequestration
B-cell
Secondary thrombocytopenia
o
b. Qualitative
disorders
ACQUIRED HEMOSTATIC DEFECTS
a. Quantitative
Autoimmune malignancies
QUANTITATIVE DEFECTS
Quantitative Platelet Defects Inherited Thrombocytopenia
Heparin-induced thrombocytopenia
1.
Deficiency of cyclooxygenase Abnormalities in platelet actin, myosin, cytoskeletal proteins, and enzymes involved in various aspects of platelet metabolism Treatment: DDAVP- mild bleeding Platelet transfusion
o
A. Qualitative disorders
Other intrinsic platelet defects:
Idiopathic thrombocytopenia
o
GRAY PLATELET SYNDROME
o
o
3.
Immune-mediated disorders
secondary to viral infections (HIV infection) or use of drugs and disorders (thrombotic thrombocytopenic purpura and hemolytic uremic syndrome)
corticosteroids
IV gamma globulin
anti-D immunoglobulin in patients who are Rhpositive
Gamma globulin and anti-D immunoglobulin
rapid onset
Survival of transfused platelets
o
Short
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Primary Immune Thrombocytopenia
known as purpura(ITP)
idiopathic
o
In children
o
acute and short lived
o
typically follows a viral illness
thrombocytopenic
o
gradual in onset
o
chronic
o
no identifiable cause
Circulating platelets: young functional
Bleeding o
In adults
less for a given platelet count than when there is failure of platelet production
fall 5 to 7 days after heparin has been started re-exposure o decrease in count may occur within 1 to 2 days should be suspected if the platelet count falls to <100,000/L or drops by 50% from baseline in a patient receiving heparinmore common with full-dose unfractionated heparin (1 to 3%) occur with prophylactic doses or with low molecular weight heparins approximately17% of patients receiving unfractionated heparin and 8% of those receiving low molecular weight heparin o develop antibodies against PF4 with high incidence of thrombosis may be arterial or venous absence of thrombocytopenia in these patients o does not preclude the diagnosis of HIT o
Pathophysiology o
involve both impaired platelet production and T cell– mediated platelet destruction
Diagnosis of HIT
Drug-Induced Immune Thrombocytopenia
Treatment
o
Withdrawal of the offending drug
Hastens recovery
o
Corticosteroids
o
Gamma globulin
o
Anti-D immunoglobulin
uses either a serotonin release assay or enzyme-linked immunosorbent assay (ELISA) o serotonin release assay o highly specific but not sensitive o ELISA has a low specificity o negative ELISA result essentially rules out HIT
Initial treatment of HIT o
Goal to stop heparin start with alternative anticoagulant Alternative anticoagulants are primarily thrombin inhibitors o Lepirudin
Management of Idiopathic Purpura (ITP) in Adults
Thrombocytopenic
First Line: a.Corticosteroids: The majority of patients respond, but only a few long term. b.IV immunoglobulin: Indicated with clinical bleeding, along with platelet transfusion, and when condition is steroid unresponsive. Response is rapid but t ransient. c. Anti-D immunoglobulin: Active only in Rh-positive patients before splenectomy. Response is transient SPLENECTOMY: Open or laparoscopic. Criteria include severe thrombocytopenia, high risk of bleeding, and continued need for steroids. Treatment failure may be due to retained accessory splenic tissue.
Heparin-Induced Thrombocytopenia (HIT)
form of drug-induced immune thrombocytopenia immunologic disorder o antibodies against PF4 affect platelet activation and endothelial function with resultant thrombocytopenia and intravascular thrombosis platelet count
Dave.Linelle.Deane.Mhe.Te.Paul
o
In Canada and Europe, danaparoid also is available
heparinoid that has approximately 20% cross reactivity with HIT antibodies (vivo < vitro)
large vWF molecules interact with plateletsactivation inhibition of metalloproteinase enzyme (ADAMTS13) characterized by thrombocytopenia microangiopathic hemolytic anemia fever renal and neurologic signs or symptoms finding of schistocytes on a peripheral blood smear aids in the diagnosis
b. Rituximab, an anti-CD20 monoclonal antibody: Acts by eliminating B cells.
Thrombopoietic agents: A new class of drugs for patients with impaired production of platelets rather than accelerated destruction of platelets. Second-generation drugs still in clinical trials include AMG531 and eltrombopag.
Bivalirudin
a. Patients for whom firstand second-line therapies fail are considered to have chronic ITP. The objective in this subset of patients is to maintain the platelet count >20–30 x 109/L and to minimize side effects of medications.
Alternative medications producing mixed results and a limited response: Danazol, cyclosporine A, dapsone, azathioprine, and vinca alkaloids.
o
Thrombotic Thrombocytopenic Purpura (TTP)
Third Line:
c.
Argatroban
Danaparoid
Second Line: a.
o
most effective treatment for TTP o
plasmapheresis
RITUXIMAB
Monoclonal antibody against the CD20 protein on B lymphocytes Immunomodulatory therapy against (majority:autoimmune mediated)
acquired
TTP
Hemolytic Uremic Syndrome (HUS)
often occurs secondary to infection
o
Escherichia coli 0157:H7
o
other Shiga toxin– producing bacteria
metalloproteinase
o
normal
usually is associated with some degree of renal fail ure
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many patients requiring renal replacement therapy
o
less frequent neurologic symptoms
o
TTP and HUS developed by patients w/
Autoimmune diseases (SLE)
HIV infection
in association with certain drugs (such as ticlopidine, mitomycin C, gemcitabin Associated with immunosuppressive agents (such as cyclosporine and tacrolimus)
Fever
Infection
Hepatosplenomegaly
Presence of antiplatelet alloantibodies decrease the transfusions
o
they have normal total body platelet mass
effectiveness
of
occurs with massive transfusion (>10 units of packed red blood cells)
Uremia
larger fraction of the platelets are in the enlarged spleen
may be associated with increased bleeding time and impaired aggregation
Platelet survival: mildly decreased
Bleeding is less than anticipated from the count
Defective aggregation and platelet secretion
Platelet transfusion does not increase the platelet count as much as it would in a normal person o
because transfused platelets sequestered in the spleen
are
do not correct the thrombocytopenia of hypersplenism caused by portal hypertension
QUALITATIVE PLATELET DEFECTS Thrombocytopenia
reduced platelet count due to a variety of disease processes marrow usually demonstrates a normal or increased number of megakaryocytes also occurs in surgical patients as a result of massive blood loss and replacement with product deficient in platelets
o
o
o
acetylation
Glycoprotein IIB/IIIA Inhibitors
of
platelet
For each drugs (mentioned above) o
a period of approximately 7 days is required from the time the drug is stopped until an elective procedure can be performed
Other disorders function
associated
with
Uremia
Myeloproliferative Disorders o o
abnormal
platelet
intrinsic to the platelets usually improves if the platelet count can be reduced to normal with chemotherapy surgery
should be delayed until the count has been decreased
count of >50,000/ L generally requires no specific therapy
These
patients are at risk for both bleeding and thrombosis
use of human leukocyte antigen (HLA)– compatible platelets coupled with special processors has proved effective
to increase the platelet count in surgical patients with underlying thrombocytopenia
myelofibrosis
Dipyridamole
Monoclonal Gammopathies o
o
administered preoperatively o
o
Both aspirin and clopidogrel irreversibly inhibit platelet function, clopidogrel through selective irreversible inhibition of ADP-induced platelet aggregation
Platelets
polycythemia vera
Clopidogrel
management is contingent on the extent and cause of platelet reduction
In patients whose thrombocytopenia is refractory to standard platelet transfusion
o
In patient for whom an elective operation is being considered o
reduced number of megakaryocytes in the marrow
thrombocythemia
through irreversible prostaglandin synthase
heparin administration (in cardiac and vascular disorders)
In patients with leukemia or uremia and receiving cytotoxic therapy
o
Aspirin
induced by
o
most common abnormality of hemostasis bleeding in the surgical patient
o
In patients with
Drugs that interfere with platelet function by design o
can be corrected by hemodialysis or peritoneal dialysis
similarly
Splenectomy
platelet
Impaired ADP-stimulated aggregation
accompanies thrombocytopenia
Decreased effectiveness of platelet transfusion
In patients with hypersplenism:
platelets
Impaired function
important cause of thrombocytopenia sequestration of platelets in an enlarged spleen (related to portal hypertension, sarcoid, lymphoma, or Gaucher's disease)
10
increase the circulating platelet count by approximately 10,000/ L in the average 70kg person
o
Sequestration
with approx. 5.5 x
result of interaction of the monoclonal protein platelets treatment with plasmapheresis
chemotherapy,
or
with
occasionally
to lower the amount of monoclonal protein
Liver Disease
One unit of platelet concentrate
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Administration of desmopressin acetate/ dialysis o
corrects platelet dysfunction in surgical patients Acquired Hypofibrinogenemia
Disseminated Intravascular Coagulation (DIC)
o
Characterized by the intravascular activation of coagulation with the loss of localization arising from different causes. It can originate from and cause damage to the microvasculature, , can produce organ dysfunction Additional causes Malignancy Organ injury (such as severe pancreatitis) Liver failure o Certain vascular abnormalities (such as large o aneurysms) Snakebites o Illicit drugs o Transfusion reactions o Transplant rejection o Sepsis o Accompanies sepsis and may be associated with multiple organ failure
o o o o
o
o o
o
o
Diagnosis
inciting cause with associated thrombocytopenia
o
prolongation of the PT
o
low fibrinogen level elevated levels of fibrin markers (fibrin degradation products, D-dimer, soluble fibrin monomers)
facets of treatment o
o
relieving the patient's causative primary medical or surgical problem maintaining adequate perfusion
heparin therapy has been proposed
Specific injuries (ofDIC) o
central nervous system injuries with embolization of brain matter
o
fractures with embolization of bone marrow
o
amniotic fluid embolization
Excessive Thrombin Generation
leads to microthrombus formationconsumption and depletion of coagulation factors and platelets classic picture of diffuse bleeding Primary Fibrinolysis
o
o
caused by acquired hypofibrinogenic state in the surgical patient occur in patients after prostate resection when urokinase is released during surgical manipulation of the prostate or in patients undergoing extracorporeal bypass Fibrinolytic bleeding dependent on the concentration of breakdown products in the circulation Synthetic amino acid-aminocaproic acid interferes with fibrinolysis by inhibiting plasminogen activation Myeloproliferative Diseases
o
o
o
o
o
o
o
o
Polycythemia - particularly with marked thrombocytosis presents a major surgical risk Operations are considered only for the most grave surgical emergencies
Dave.Linelle.Deane.Mhe.Te.Paul
Defer operation until medical management has restored normal blood volume, hematocrit level, and platelet count Spontaneous thrombosis complication of polycythemia vera explained in part by increased blood viscosity increased platelet count increased tendency toward stasis Myeloid metaplasia frequently represents part of the natural history of polycythemia vera Approximately 50% of patients with myeloid metaplasia are postpolycythemic Thrombocytosis reduced by the administration of hydroxyurea or anagrelide Elective surgical procedures should be delayed until the institution of appropriate treatment hematocrit level is kept below 48% and platelet count under 400,000/ L In emergency procedure phlebotomy and blood replacement with lactated Ringer's solution may be beneficial
Coagulopathy of Liver Disease Liver Plays a key role in hemostasis o responsible for the synthesis of many of the coagulation factors Most common coagulation abnormalities associated with liver dysfunction: thrombocytopenia o o impaired humoral coagulation function manifested as prolongation of the PT increase in the International Normalized o Ratio (INR)
Thrombocytopenia in Patients with Liver Disease typically related to hypersplenism reduced production of thrombopoietin immune-mediated destruction of platelets Immune-mediated thrombocytopenia o may also occur in cirrhotic patients (w/ hepatitis C and primary biliary cirrhosis) Ameliorate thrombocytopenia o before therapy, the actual need for correction should be strongly considered o In general, correction based solely on a low platelet count should be discouraged
Patients with Hypersplenism the total body platelet mass is basically normal abnormally high proportion of the platelets Less bleeding is seen than would be anticipated from the platelet count because some of the sequestered platelets can be released into the circulation Splenectomy o less well accepted option is splenectomy or splenic embolization reduce hypersplenism reduced splenic blood flow reduce portal vein flow with subsequent portal vein thrombosis Results are mixed after transjugular intrahepatic portosystemic shunt (TIPS)
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o
treatment of thrombocytopenia should not be the primary indication for a TIPS procedure
Thrombopoietin primary stimulus for thrombopoiesis responsible for some cases of thrombocytopenia in cirrhotic patients o should be withheld f or invasive procedures and surgery Platelet transfusions mainstay of therapy effect typically lasts only several hours
Other Diseases Paraprotein Disorders
production of abnormal globulin or fibrinogen that interferes with clotting or platelet function
IgM IgG or IgA Cryoglobulin cryofibrinogen
Administration of Il-11 potential alternative stimulates proliferation of hematopoietic stem cells and megakaryocyte progenitors Most studies using interleukin-11 have been in patients with cancer Significant side effects limit its usefulness
Decreased production or increased destruction coagulation factors and vitamin K deficiency contribute to a prolonged PT increased INR in patients with li ver disease
of
Treatment: Chemotherapy -effective in lowering the paraproteins of macroglobulinemia and myeloma, Plasmapheresis - usually removes Cryoglobulins and cryofibrinogens
Correction of Coagulopathy reserved for treatment of active bleeding and prophylaxis for invasive procedures and surgery w/ liver disease, treated with FFP Complete correction is not possible Fibrinogen level is <100 mg/dL Administration of cryoprecipitate may be helpful Cryoprecipitate o source of factor VIII for the rare patient with a low factor VIII level
Coagulopathy of Trauma
o
Causes Acidosis o Hypothermia o o Dilution of coagulation factors Only patients in shock arrive coagulopathic and that it is the shock that induces coagulopathy through systemic activation of anticoagulant and fibrinolytic pathways hypoperfusion causes activation of thrombomodulin on the surface of endothelial cells
Circulating thrombin complexes with thrombomodulin. induces an anticoagulant state through activation of protein C enhances fibrinolysis by deinhibition of tPA through the consumption of plasminogen activator inhibitor 1
Acquired Coagulation Inhibition Antiphospholipid Syndrome (APLS)
most common acquired disorder of coagulation inhibition lupus anticoagulant and anticardiolipin antibodies are present these antibodies are associated with either arterial or venous thrombosis APLS is very common in patients with systemic lupus erythematosus (SLE), and associated with rheumatoid arthritis and Sjörgen’s Syndrome Hallmark is prolonged aPTT in vitro but an increased risk of thrombosis in vivo
Dave.Linelle.Deane.Mhe.Te.Paul
Hypersplenism associated with platelet sequestration and platelet survival is mildly decreased total body platelet mass essentially normal, but a much larger fraction of the platelets than normal are in the enlarged spleen Bleeding is less anticipated because sequestered platelets can be mobilized and enter the circulation Platelet transfusion not helpful will end up in spleen
ACQUIREDANTICOAGULATION HEMOSTATIC DEFECTS AND BLEEDING
or
Waldenström's macroglobulinemia multiple myeloma liver disease (especially hepatitis C) or autoimmune diseases
Spontaneous bleeding - complication of anticoagulant therapy with: low molecular weight heparins o o factor Xa inhibitors To reduce bleeding with continuous infusion of heparin: aPTT must be regulated between 1.5 o and 2.5 times the upper limit of normal Therapeutic anticoagulation is more reliably achieved with low molecular weight heparin laboratory testing is not routinely used to o monitor dosing of these agents An exaggerated response to oral anticoagulants may occur if dietary vitamin K i s inadequate. Anticoagulant effect of the warfarin is reduced in patients receiving barbiturates, contraceptives, other estrogen-containing compounds, corticosteroids, ACTH o Reduced anticoagulant dosage should be instituted after discontinuance of any of these drugs. Medications known to increase the effect of oral anticoagulants Phenylbutazone o o Clofibrate (cholesterol-lowering agent) a variety of antibiotics (particularly the o Cephalosporins) Anabolic steroids (norethandrolone) o Amiodarone o o Glucagons L-thyroxine o Quinidine o Onset of hematuria or melena in the patient receiving anticoagulants should be investigated may unmask underlying tumors. PE reveals other signs of bleeding, such o as ecchymoses, petechiae, or hematoma
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CNS and eye surgeries minor bleeding poses a great problem: anticoagulants should be discontinued, and, if necessary, reversed Rebound phenomenon – risk of thrombotic complications is increased when anticoagulation therapy is discontinued suddenly
MECHANICAL PROCEDURES Digital pressure is applied to an artery Pressure proximal to an area of bleeding to reduce profuse bleeding often effective and has the advantage of being less traumatic than any hemostatic clamp cannot be used permanently Pringle maneuver process by which a tourniquet is used to occlude the hepatic artery and portal vein in the hepatoduodenal ligament as a method of controlling bleeding from a transected cystic artery or the raw surface of the liver Hemostatic represents a temporary Clamps mechanical device to stem bleeding disadvantage: result in damage to the intimal wall of a blood vessel Ligature or replaces the hemostat as a Hemoclip permanent method of effecting hemostasis of a single disrupted vessel. When a small vessel was transected, a simple ligature is sufficient. For large arteries with pulsation and longitudinal motion, a transfixion suture to prevent slipping is indicated.
When the aPTT is <1.3 times control in a heparinized patient, or when the INR is<1.5 in a patient on warfarin, meticulous surgical technique is mandatory Certain surgical procedures should not be performed in the face of anticoagulation; Procedures requiring blind needle introduction should be avoided
Management:
Discontinuation of heparin may be sufficient if the operation can be delayed for several hours For more rapid reversal 1 mg of protamine sulfate for every 100 units of heparin most recently administered The reversal of warfarin may take several hours; more rapid reversal can be accomplished with fresh-frozen plasma or prothrombin complex concentrate (Konyne or Proplex) Parenteral administration of vitamin K indicated in elective surgical treatment of patients with bili ary obstruction or malabsorption
Sutures
Excessive Bleeding Associated With Cardiopulmonary Bypass Triggering factors: excessive fibrinolysis o o abnormal platelet functions Laboratory evaluation tests may include: o INR, aPTT, CBC, platelet count, peripheral blood smear examination and measurement of fibrin degradation products Treatment may include: Administration of platelets o Protamine o o ε- aminocaproic acid aprotinin o desmopressin acetate o
Local Hemostasis The goal is to prevent or interrupt the flow of blood from a disrupted vessel that has been incised or transected. May be accomplished by: interrupting the flow of blood to the o involved area direct closure of the blood vessel wall o defect The techniques are classified as: 1. MECHANICAL 2. THERMAL 3. TOPICAL HEMOSTATIC AGENTS
Harmonic Scalpel
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Required when the bleeding is from a lateral defect in a large vessel represent foreign material, and selection is based on their intrinsic characteristics and the state of the wound Non-absorbable sutures, such as silk, polyethylene, and wire evoke less tissue reaction Absorbable sutures such as catgut, polyglycolic (Dexon), and polyglactin (Vicryl) preferable for grossly infected wounds because the nonabsorbable material can lead to extrusion or sinus formation Monofilament wire and coated sutures have an advantage over multifilament material in the presence of infection because the latter tends to fragment and permit sinus formation an instrument that cuts and coagulates tissue via vibration at 55 kHz A device that converts electrical energy into mechanical motion The motion of the blade causes collagen molecules within the tissue to become denatured forming a coagulum advantageous in performing thyroidectomy, hemorrhoidectomy, transsection of the short gastric veins during splenectomy, and in transecting hepatic parenchyma
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THERMAL AGENTS Heat
Local Cooling (decreased temp)
achieves hemostasis by denaturation of protein that results in coagulation of large areas of tissue ACTUAL CAUTERYheat is transmitted from the instrument by conduction directly to the tissue ELECTROCAUTERY heating occurs by induction from an alternating current source DIRECT CURRENT (20- to 100mA range) have successfully controlled diffuse bleeding from a raw surface; because the protein moieties and cellular elements of blood have a negative surface charge, they are attracted to a positive pole where a thrombus is formed has been applied to control bleeding from the eroded mucosa of the esophagus and stomach. Direct cooling with iced saline is effective and acts by increasing the local intravascular hematocrit and by causing vasoconstriction of the arterioles EXTREME COOLING, i.e., cryogenic procedures, have been applicable in gynecology and as a method of destroying hepatic metastases
promoting inflammation or tissue necrosis particularly helpful in patients who have received heparin or who have deficiencies in coagulation (e.g., hemophilia or von Willebrand's disease)
Purified gelatin solution
can be prepared into several vehicles, including powders, sponges or foams, and sheets or films Hygroscopic - absorbing many times its weight in water or liquid effectively metabolized and degraded by proteinases in the wound bed over a period of 4 to 6 weeks provides effective hemostasis for operative fields with diffuse smallvessel oozing Thrombin may be applied to boost hemostasis relatively Advantages: inexpensive, readily available, pliable, and easy to handle Disadvantages: implanted gelatin can serve as a nidus for infection
TRANSFUSION
TOPICAL HEMOSTATIC AGENTS can be classified based on their mechanism of action and include physical or mechanical, caustic, biologic, and physiologic agents Some agents induce protein coagulation and precipitation occlusion of small cutaneous vessels Others take advantage of later stages in the coagulation cascade activating biologic responses to bleeding
BACKGROUND th
Late 19 century
1900
The ideal topical hemostatic agent: With significant hemostatic action o Has minimal tissue reactivity o Is nonantigenic o Biodegrades in vivo o Provides ease of sterilization o Low in cost o Can be tailored to specific needs o
Thrombinderivative products
Fibrin sealants
direct the conversion of fibrinogen to fibrin, aiding in clot formation takes advantage of natural physiologic processes avoiding foreign body or inflammatory reactions wound bed is not disturbed thrombin entry into larger-caliber vessels can result in systemic exposure to thrombin with a risk of disseminated intravascular clotting or death prepared from cryoprecipitate (homologous or synthetic) have the advantage of not
Dave.Linelle.Deane.Mhe.Te.Paul
1939
Late 1970s
social acceptance of human blood replacement therapy Introduction of ABO blood grouping (Dr. Karl Landsteiner) Rh grouping (Dr. Levine & Dr. Stetson) Whole blood was considered the standard in transfusion
REPLACEMENT THERAPY
Typing and Cross Matching serologic compatibility is established routinely for the recipients' and donors' A, B, O, and Rh groups in selecting blood for transfusion cross-matching between the donors' red blood cells and the recipients' sera (the major cross-match) is performed as a rule, Rh-negative recipients should be transfused only with Rh-negative blood (If the recipient is an elderly male who has not been transfused previously, the administration of Rh-positive blood is acceptable if Rh-negative blood is not available anti-Rh antibodies form within several weeks of transfusion anti-Rh antiserum (RhoGAM) should be given if Rhpositive products have been given to an Rh-negative patient
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Rh-positive blood should not be transfused to Rhnegative females who are capable of child-bearing administration of hyperimmune anti-Rh globulin to Rhnegative women shortly before or after childbirth largely eliminates Rh disease in subsequent offspring for patients receiving repeated transfusions, serum drawn not more than 72 hours before cross-matching should be used for matching with cells of the donor (Emergency transfusion can be accomplished with type O blood) O-negative and type-specific red blood cells are equally safe for emergency transfusion problems are associated with the administration of four or more units of O-negative blood because there is a significant increase in the risk of hemolysis for patients with clinically significant cold agglutinins, blood should be administered through a blood warmer (If these antibodies are present in high titer, hypothermia is contraindicated) for patients with multiple transfusion and who have developed alloantibodies, or who have autoimmune hemolytic anemia with pan-red blood cell antibodies, typing and cross-matching is often difficult, and sufficient time should be allotted preoperatively to accumulate blood that might be required during the operation cross-matching should always be performed before the administration of dextran because it interferes with the typing procedure for autologous transfusion, up to 5 units can be collected for subsequent use during elective procedures patients can donate blood if their hemoglobin concentration exceeds 11 g/dL or if the hematocrit is greater than 34% first procurement is performed 40 days before the planned operation and the last one is performed 3 days before the operation donations can be scheduled at intervals of 3 to 4 days recombinant human erythropoietin (rHuEPO) accelerates generation of red blood cells and allows for more frequent harvesting of blood
Banked Whole Blood shelf life extended to 40 ± 5 days at least 70% of the transfused erythrocytes remain in the circulation for 24 hours after transfusion and are viable rarely indicated and rarely available changes in the red blood cells that occur during storage include reduction of intracellular ADP and 2,3diphosphoglycerate (2,3-DPG), which alters the curve of oxygen dissociation from hemoglobin, decreasing the function of oxygen transport along with the clotting factors, only factor V and VIII are stable in banked blood pH decreases from 7.00 to 6.68, and the lactic acid level increases from 20 to 150 mg/dL within 21 days of storage potassium concentration rises steadily to 32 mEq/dL, and the ammonia concentration rises from 50 to 680 mg/dL at the end of 21 days Fresh Whole Blood blood administered within 24 hours of its donation rarely indicated must be administered untested because of the time required for testing for infectious disease 1 unit of platelet concentrate has more viable platelets than 1 unit of fresh blood poor source of platelets and factor VIII
Dave.Linelle.Deane.Mhe.Te.Paul
Packed Red Blood Cells and Frozen Red Blood Cells product of choice for most clinical situations concentrated suspensions of red blood cells can be prepared by removing most of the supernatant plasma after centrifugation preparation reduces but does not eliminate reaction caused by plasma components (also reduces the amount of sodium, potassium, lactic acid, and citrate administered) provides oxygen-carrying capacity frozen red blood cells are not available for use in emergencies (used for patients who are known to have been previously sensitized) improved red blood cell viability and the ATP and 2,3DPG concentrations are maintained Leukocyte- Reduced and LeukocyteReduced/Washed Red Blood Cells prepared by filtration eliminate 99.9% of the WBCs and most of the platelets (leukocyte-reduced red blood cells), and, if needed, by additional saline washing (leukocytereduced/washed red blood cells) leukocyte-reduction prevents almost all febrile, nonhemolytic transfusion reactions (fever and/or rigors), alloimmunization to HLA class I antigens, and platelet transfusion refractoriness and cytomegalovirus transmission washed, leukocyte-reduced red blood cells are usually given only to patients who have had reactions (rash, urticaria, anaphylaxis) to unwashed red blood cells Platelet Concentrates indicated for thrombocytopenia caused by massive blood loss and replacement with platelet-poor products; and by inadequate production also given to patients with qualitative platelet disorders preparations should be used within 120 hours of donation 1 unit of platelet concentrate = 50 mL can transmit infectious diseases and account for allergic reactions similar to those caused by blood transfusion elevate the platelet count to the range of 50,000 to 100,000/microL when treating bleeding caused by thrombocytopenia or preparing some thrombocytopenic patients for an operation leukocyte reduction through filtration prevents HLA alloimmunization patients who become alloimmunized through previous transfusion, or those patients who are refractory from sensitization through prior pregnancies, HLA-matched platelets can be used platelet transfusion thresholds can safely be lowered in patients without signs of hemostatic deficiency and who have no history of poor tolerance to low platelet counts multiple platelet transfusions predispose to multiorgan failure and mortality is dose-dependent shelf life of platelets: 120 hrs from time of donation Frozen Plasma and Volume Expanders frozen plasma prepared from freshly donated blood is the standard source of the vitamin K–dependent factors (and is the only source of factor V) factor V is less stable than the vitamin K–dependent factors) risk of infectious disease is the same whether FFP, whole blood, or red blood cells is administered Lactated Ringer's solution or buffered saline solution administered in amounts 2 to 3 times the estimated blood loss is effective and associated with fewer complications
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Dextran or a combination of lactated Ringer's solution and normal serum albumin are preferred for rapid volume expansion commercially available dextran should not be administered more than 1 L/d because of prolonged bleeding time and consequent hemorrhage low molecular weight dextran (30–40,000 Da) possesses a higher colloidal pressure than plasma and effects some reversal of erythrocyte agglutination
Concentrates and Recombinant DNA Technology antihemophilic concentrates are prepared from plasma and are available for treatment of factor VIII or factor IX deficiency various concentrates are 20 to 30 times as potent as an equal volume of FFP concentrated albumin of 25 g can be administered to provide the equivalent of 500 mL of plasma and has the advantage of being hepatitis-free
Replacement of Clotting Factors transfusion of platelets and/or proteins contributing to coagulation may be indicated in specific patients before or during an operative procedure
Table for replacement of clotting factors (refer to the last page) Specific Indications Massive Transfusion
Human Polymerized Hemoglobin (Polyheme) universally compatible immediately available disease-free oxygen-carrying resuscitative fluid that has been successfully used in massively bleeding patients when red blood cells were not transfused absence of blood-type antigens (no cross-match needed) and viral infections long-term stability disadvantages though are shorter half-life in the bloodstream and cardiovascular complications
Percentage of Original Blood Volume Remaining in a Patient with a 5-L Blood Volume Transfused with 500-mL Units Magnitude of Hemorrhage and Transfusion
INDICATIONS FOR REPLACEMENT OF BLOOD AND ITS ELEMENTS
General Indications Improvement in Oxygen-Carrying Capacity
oxygen-carrying capacity is chiefly a function of RBCs transfusion should be withheld when anemia can be treated by specific therapy, such as erythropoietin acute anemias are more disabling than chronic anemia because patients with chronic anemia have undergone an adjustment to the deficiency moderate drop in the hematocrit level and transfusions are not indicated to correct the physiologic anemia in pregnancy if an operation is required correction of chronic anemia before surgical intervention is often not necessary hemoglobin value of less than 10 g/dL or a hematocrit level less than 30% indicates a need for preoperative red blood cell transfusion cardiac output does not increase significantly in healthy individuals until the hemoglobin value decreases to approximately 7 g/dL patients with chronic anemia and a hemoglobin value of less than 7 g/dL in whom intraoperative bleeding is not anticipated do not require a transfusion preoperatively blood volume can be replaced with dextran solution or lactated Ringer's solution with a reduction of the hemoglobin value to levels below 10 g/dL human polymerized hemoglobin can be used to increase oxygen-carrying capacity whole blood substitute, Fluosol-DA, has been proposed as a solution with increased oxygen-handling capability
Dave.Linelle.Deane.Mhe.Te.Paul
entails a single transfusion greater than 2500 mL or 5000 mL transfused over a period of 24 hours circulatory overload or DIC might occur dilutional thrombocytopenia, impaired platelet function, and deficiencies of factors V, VIII, and XI can also be encountered routine alkalization is not advisable because this could have an adverse effect on the hemoglobin dissociation curve and also is accompanied by an increased sodium load
Situation
1 Blood Volume (10 Units)
2 Blood Volume (20 Units)
3 Blood Volume (30 Units)
Best
37
14
5
Usual
25–30
10
2–4
Worst
18
3
0.4
"best" situation requires simultaneous and equal replacement during hemorrhage; "worst" situation means initial loss of one-half blood volume not replaced until the hemorrhage has stopped
citrate toxicity from the use of stored blood may result in young children, in patients with severe hypotension, or in patients with liver disease (toxicity is related to an excessive binding of ionized calcium) use of stored blood also provides a potassium load, but there are no effects in the face of normal renal function when large volume transfusions are administered, a heat exchanger should be used because hypothermia can cause a decrease in cardiac rate and output and blood pH use of blood from multiple donors increases the risk of hemolytic reaction as a consequence of incompatibility when massive transfusions are administered, the pH, blood gases, and potassium should be measured regularly and abnormalities corrected immediately if diffuse bleeding is noted, coagulation tests and platelet counts should be measured and deficiencies corrected
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METHODS OF ADMINISTERING BLOOD
o
Routine Administration rate of transfusion depends upon the patient's status Usually 5 mL/min is administered for the first minute, after which 10 to 20 mL/min is given when there is marked oligemia, 500 mL can be given within 10 minutes and a second 500 mL also can be given within 10 minutes approximately 1500 mL/min can be administered through two 7.5-F catheters Other Methods blood can be instilled intraperitoneally or into the medullary cavity of long bones and the sternum approximately 90% of red blood cells injected intraperitoneally enter the circulation, but uptake is n ot complete for at least a week intraoperative autotransfusion is a potentially lifesaving adjunct roughly 250 mL of blood can be retrieved, washed or filtered, and returned to the patient over a 5-minute period another approach to anticipated intraoperative large blood losses is hemodilution (at the onset of the procedure, RBCs are removed while the intravascular volume is maintained with crystalloid or colloid) reduced blood viscosity improves the microcirculatory perfusion removed blood can then be retransfused during the operation to replace lost blood
o o o
o
o
o
o o
Respiratory Complications associated with transfusion-associated circulatory overload avoidable complication occurs with rapid infusion of blood, plasma expanders, and crystalloids esp. in older patients with underlying heart disease Central venous pressure monitoring should be considered whenever large amounts of fluid are administered
o o
COMPLICATIONS OF TRANSFUSION
o o
Nonhemolytic Reactions/Febrile Reactions increase in temperature [>1°C (1.8°F)] associated with a transfusion
o
o
o
o o
o o o
CAUSE: Preformed cytokines in donated blood and recipient antibodies reacting with donated antibodies PREVENTION:use of leukocyte-reduced and/or out of date blood products Acetaminophen/Paracetamol- reduces the severity of the reaction. Bacterial contamination of infused blood is rare. CLINICAL MANIFESTATIONS Systemic Signs fever and chills tachycardia hypotension GI Symptoms abdominal cramps vomiting diarrhea Hemorrhagic Manifestations hemoglobinemia hemoglobinuria disseminated intravascular coagulation UPON SUSPECTED DIAGNOSIS: STOP the transfusion Have the donated blood cultured Emergency treatment administration of oxygen adrenergic blocking agents antibiotics Allergic Reactions relatively frequent (~1% of all transfusions) can occur after the administration of any blood product
o o o
CLINICAL MANIFESTATION rise in venous pressure dyspnea cough rales at the lung bases TREATMENT initiating diuresis slowing the rate of blood administration minimizing delivery of fluids while blood products are being transfused
Syndrome of Transfusion-related Acute Lung Injury (TRALI) noncardiogenic pulmonary edema related to transfusion can occur with the administration of any plasma containing blood product o o o o o o o
o o
o o
o
Dave.Linelle.Deane.Mhe.Te.Paul
CLINICAL MANIFESTATIONS usually mild rash urticaria fever (alloccurring within 60 to 90 minutes of transfusion) anaphylactic shock - rare CAUSE transfusion of antibodies from hypersensitive donors transfusion of antigens to which the recipient is hypersensitive TREATMENT AND PROPHYLAXIS antihistamines epinephrine or steroids in more serious cases
CLINICAL MANIFESTATIONS similar to those of circulatory overload dyspnea hypoxemia fever rigors bilateral pulmonary infiltrates on CXR occurs within 1 to 2 hours of transfusion, but virtually always before 6 hours CAUSE not well established thought to be related to anti-HLA or anti–human neutrophil antigen antibodies in transfused blood that primes neutrophils in the pulmonary circulation RISK FACTORS Multiparity of the donor - major risk factor Female donors TREATMENT discontinuation of any transfusion
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o o
notification of the transfusion service provision of pulmonary support supplemental oxygen mechanical ventilation -
o o o o o
o o
o
o o
o o
Hemolytic Reactions high index of suspicion is needed to make the diagnosis LABORATORY CRITERIA hemoglobinuria serologic findings that show incompatibility of the donor and recipient blood (+) Coombs' test presence of transfused cells coated with patient antibody (diagnostic) GENERAL TREATMENT STOP the transfusion immediately sample of the recipient's blood drawn and sent along with the suspect unit to the blood bank Monitor Urine output Maintain adequate hydration to prevent precipitation of hemoglobin within the tubules
recurrent anemia Jaundice decreased haptoglobin levels low-grade hemoglobinemia and hemoglobinuria (+) Coombs' test
Transmission of Disease Diseases that can be transmitted by t ransfusion: Malaria Chagas' disease Brucellosis Syphilis (very rarely) Malaria (most common: Plasmodium malariae) incubation period: 8 to 100 days initial manifestations shaking chills spiking fever hepatitis C HIV-1 Hepatitis B Prion disorders (e.g., Creutzfeldt-Jakob disease)
Acute Hemolytic Reactions TEST OF HEMOSTASIS AND BLOOD COAGULATION
occur with the administration of ABOincompatible blood
o o
o o o o o o o o o o o o
o
o
fatal in up to 6% of cases CONTRIBUTING FACTORS technical or clerical errors in the laboratory administration of blood of the wrong blood type CLINICAL MANIFESTATIONS intravascular destruction of red blood cells hemoglobinemia hemoglobinuria pain at the site of transfusion facial flushing back (flank) chest pain fever respiratory distress hypotension tachycardia for anesthetized patients: diffuse bleeding hypotension DIC can be initiated by activation of factor XII and complement by antibody-antigen complexescoagulation cascade Acute Renal Insufficiency results from the toxicity associated with free hemoglobin in the plasma tubular necrosis precipitation of hemoglobin within the tubules
Delayed Hemolytic Reactions occur 2 to 10 days after transfusion occur when an individual has a low antibody titer at the time of transfusion but the titer increases after transfusion as a result of an anamnestic response Reactions to non-ABO antigens i nvolve immunoglobulin G–mediated clearance by the reticuloendothelial system. do not usually require specific intervention
o o o o
CLINICAL MANIFESTATIONS extravascular hemolysis mild anemia indirect (unconjugated) hyperbilirubinemia fever
Dave.Linelle.Deane.Mhe.Te.Paul
Carefully review the patient's clinical history and drug use, and basic laboratory testing. Common screening laboratory testing platelet count PT or INR Aptt normal platelet count : 150,000 to 400,000/ µL. bleeding or thrombotic complications Platelet counts >1,000,000/µL Increased bleeding complications may be seen with major surgical procedures when the platelet count is<100,000/ L minor surgical procedures when counts are <50,000/ L Spontaneous hemorrhage: when count falls below 20,000/ L. o PT and aPTT - variations of plasma recalcification times initiated by the addition of a thromboplastic agent PT reagent o contains thromboplastin and Ca o when added to plasma, leads to the formation of a fibrin clot PT test o measures the function of factors I, II, V, VII, and X VII -shortest half-life of the coagulation o Factor factors, and its synthesis is vitamin K dependent. suited to detection of abnormal coagulation o best caused by vitamin K deficiencies and warfarin therapy
Due to variations in thromboplastin activity, it can be difficult to accurately assess the degree of anticoagulation on the basis of PT alone determination of the INR is now the method of o choice for reporting PT values. Sensitivity Index (ISI) is unique to o International each batch of thromboplastin and is furnished by the manufacturer tothe hematology laboratory o Human brain thromboplastin has an ISI of 1, and the optimal reagent has an ISI between 1.3 and 1.5.
aPTT reagent phospholipid substitute, activator, and calcium
o
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in the presence of plasma leads to fibrin clot formation function of factors I, II, and V of the o measures common pathway and factors VIII, IX, X, a nd XII Heparin therapy-monitored by following aPTT values, with a therapeutic target range of 1.5 to 2.5 times the control value (approx 50 to 80 seconds) Low molecular weight heparins are selective factor Xa inhibitors and may mildly elevate the aPTT, but therapeutic monitoring is not routinely recommended. bleeding time -used to evaluate platelet and vascular dysfunction Ivy bleeding time is most commonly o used determined by placing a sphygmomanometer on the upper arm and inflating it to 40 mmHg and then making a 5-mm stab incision on the fl exor surface of the forearm Time is measured to cessation of bleeding upper limit of normal bleeding time – 7 min o abnormal bleeding time suggests either platelet dysfunction (intrinsic or drug induced), vWD, or certain vascular defects replacing the template bleeding time with an in vitro test o which blood is sucked through a capillary and the platelets adhere to the walls of the capillary and aggregate o closure time in this system appears to be more reproducible than the bleeding time o correlates with bleeding in patients with vWD, primary platelet function disorders, or other platelet dysfunction disorders and patients who are taking aspirin Additional medications may significantly impair hemostatic function such as antiplatelet agents (clopidogrel and glycoprotein o IIb/IIIa inhibitors) anticoagulant agents (hirudin, chondroitin sulfate, o dermatan sulfate) thrombolytic agents (streptokinase, tPA) o If abnormal results on any of the coagulation studies cannot be explained by known medications>congenital abnormalities of coagulation or comorbid disease should be considered o
Thromboelastography (TEG) o monitors hemostasis as a dynamic process rather than revealing isolated information as in conventional coagulation screens. o measures the viscoelastic properties of blood as it is induced to clot in a lowshear environment (resembling sluggish venous flow) o patterns of change in shear elasticity allow the kinetics of clot formation and growth as well as the strength and stability of the formed clot to be determined strength and stability data- provide information o about the ability of the clot to perform the work of hemostasis o kinetic data- determine the adequacy of quantitative factors available for clot formation o sample of celite-activated whole blood is placed into a prewarmed cuvette ->suspended piston is then lowered into the cuvette -> rotated through a 4.5-degree arc backwards and forwards o Normal clot goes through an acceleration and strengthening phase
Dave.Linelle.Deane.Mhe.Te.Paul
o
o
o
o
o
o
o
o
o
fiber strands that interact with activated platelets attach to the surface of the cuvette and the suspended piston clot forming in the cuvette transmits its movement onto the suspended piston Weak clot stretches and therefore delays the arc movement of the piston, which is graphically expressed as a narrow thromboelastogram Strong clot will move the piston simultaneously and proportionally to the cuvette's movements, creating a thick thromboelastogram strength of a clot is graphically represented over time as a characteristic cigar-shaped figure
k- measure of the time from the beginning of clot formation until the amplitude of the TEG tracing reaches 20 mm and represents the dynamics of clot formation alpha angle - angle between the line in the middle of the TEG(r) tracing and the line tangential to the developing body of the TEG(r) tracing. The alpha angle represents the acceleration (kinetics) of fibrin buildup and cross-linking MA -maximum amplitude and reflects the strength of the clot, which is dependent on the number and function of platelets and the clot's interaction with fibrin MA60 - rate of amplitude reduction 60 minutes after MA and represents the stability of the clot EVALUATION OF HEMOSTATIC RISK IN THE SURGICAL PATIENT
Preoperative Evaluation of Hemostasis Several hematologic disorders may have an impact on the outcome of surgery. pre-existing anemia and oral anticoagulation therapy-common clinical situations faced by the surgeon Assessment of bleeding risk should also be considered in patients with li ver or renal dysfunction When feasible, diagnostic evaluation of the patient with previously unrecognized anemia should be carried out before surgery, because certain types of anemia (particularly sickle cell disease and immune hemolytic anemias) may have implications for perioperative management Hemoglobin levels below 7 or 8 g/dL appear to be associated with significantly more perioperative complications than higher levels Determination of the need for preoperative transfusion in an individual patient must consider factors other than the absolute hemoglobin level, including o presence of cardiopulmonary disease type of surgery o likelihood of surgical blood loss o Many patients have anemia postoperatively secondary to blood loss and hemodilution and do not necessarily require transfusion directed bleeding history- most important component of the bleeding risk assessment provide meaningful clues to the presence o of a bleeding tendency
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Patients who are reliable historians and who reveal no suggestion of abnormal bleeding on directed bleeding history and physical examination are at very low risk for having an occult bleeding disorder Laboratory tests of hemostatic o parameters is not required When the directed bleeding history is unreliable or incomplete or when abnormal bleeding i s suggested formal evaluation of hemostasis should o be performed before surgery PT, the aPTT, and the platelet count EVALUATION OF EXCESSIVE INTRAOPERATIVE OR POSTOPERATIVE BLEEDING
Excessive bleeding during or after a surgical procedure may be the result of o ineffective hemostasis o blood transfusion o undetected hemostatic defect o consumptive coagulopathy o fibrinolysis Excessive bleeding from the operative field unassociated with bleeding from other sites usually suggests inadequate mechanical hemostasis Massive blood transfusion-well-known cause of thrombocytopenia Bleeding after massive transfusion can occur due to o Hypothermia o dilutional coagulopathy o platelet dysfunction, o fibrinolysis o hypofibrinogenemia Another cause of hemostatic failure related to the administration of blood is hemolytic transfusion reaction diffuse bleeding -first sign of a transfusion reaction o release of ADP from hemolyzed red blood cells-> diffuse platelet aggregation->after which the platelet clumps are removed out of the circulation->bleeding Transfusion purpura occurs when the donor platelets are of the uncommon Pl(A1) group uncommon cause of thrombocytopenia and o an associated bleeding after transfusion The platelets sensitize the recipient, who makes antibody -> antibody then destroys the recipient's own platelets-> thrombocytopenia and bleeding may continue for several weeks. This uncommon cause of thrombocytopenia should be considered if bleeding follows transfusion by 5 or 6 days. Platelet transfusions are of little help in the management of this syndrome, because the new donor platelets usually are subject to the binding of antigen and damage from the antibody Corticosteroids may be of some help in reducing the bleeding tendency. Posttransfusion purpura is self-limited, and the passage of several weeks inevitably leads to subsidence of the problem. DIC is characterized by systemic activation of the blood coagulation system-> results in the generation and deposition of fibrin ->leading to microvascular thrombi in various organs -> contributing to the development of multiorgan failure Consumption and subsequent exhaustion of coagulation proteins and platelets due to the ongoing activation of the coagulation system may induce severe bleeding complications
Severe hemorrhagic disorders due to thrombocytopenia have occurred as a result of gramnegative sepsis pathogenesis of endotoxin-induced o thrombocytopemia- related to lability of factor V Defibrination and hemostatic failure also may occur with meningococcemia, Clostridium perfringens sepsis, and staphylococcal sepsis Hemolysis appears to be one mechanism in o sepsis leading to defibrination
From omgfacts.com:
Dave.Linelle.Deane.Mhe.Te.Paul
Anatidaephobia is the fear that somewhere in the world, there is a duck watching you. If you touch your tongue while yawning, it can stop the yawn. You're more likely to die on your way to buy a lottery ticket than you are to actually win the lottery. Women speak about 7000 words a day. The average man averages just over 2000. 'Hippopotomonstrosesquippedaliophobia' is the fear of long words. When a person is tickled, the response is actually a form of panic, as the brain interprets the tickling sensation as produced by spiders or other creepy crawlies on your skin - the uncontrollable laughter is a response to panic. Those stars and colours you see when you rub your eyes are called phosphenes. Yawning is contagious - even thinking about yawning is enough. After reading this fact, there is a 50% chance you will yawn. The total weight of all the ants on Earth is about the same as the weight of all the humans on earth. When you kiss someone for a minute, you both burn about 2.6 calories. An elephant can die from a broken heart. 'Dreamt' is the ONLY WORD in the entire English language that ends in the letters 'mt'. 'Dysania' is the state of finding it hard to get out of bed in the morning. One tablespoon of semen has approximately 20 calories. Semen also contains zinc and calcium which helps prevent tooth decay. Breathing the air in Mumbai, India for just ONE DAY, is equivalent to smoking 2.5 packs of cigarettes. According to suicide statistics, Monday is the favored day for self-destruction. If you walk and talk with someone, eventually you will synchronize your steps with each other. Albert Einstein left his first wife for his COUSIN. A strawberry is not an actual berry, but a banana is. Your earlobes line up with your nipples. (Go try!) As a punishment for misbehavior, Thai cops have to wear pink Hello Kitty armbands. Colgate faced big obstacle marketing toothpaste in Spanish-speaking countries because Colgate translates into the command 'go hang yourself.' In Topeka, Kansas it is illegal to sing the alphabet on the streets at night. It is also illegal to install a bathtub, and you may not scream in a haunted house. Justin Bieber can solve a Rubik's Cube in less than 2 minutes. Humans don't just shrink with age. They shrink EVERY DAY. ( “Uh-oh.” – Deane)
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