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Hemostasis Shaina Eckhouse 10/12/2010

Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

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Page 1: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Hemostasis

Shaina Eckhouse10/12/2010

Page 2: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Objectives

Biology of Hemostasis

Congenital Hemostasis Defects

Aquired Hemostasis Defects

Hypercoagulable States

Venous thromboembolism

Transfusion

Evaluation of the Surgical Patient at Hemostatic Risk

Page 3: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Name that Movie

Page 4: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Biology of Hemostasis

Complex process that prevents or terminates blood loss from a disrupted intravascular space

Major physiologic events Vascular constriction Platelet plug formation Fibrin formation fibrinolysis

Page 5: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Biology of Hemostasis

Vascular Constriction Initial vascular response to injury Vasoconstriction linked to platelet plug

formation TXA2 ET 5-HT Bradykinin & Fibrinopeptides

Page 6: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Biology of Hemostasis

Platelet Function 150-400K circulating platelets ~30% sequestered in the spleen Thrombopeptin, IL-1, IL-6 mediate platelet

production

Page 7: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Biology of Hemostasis

Platelets play an integral role in: Formation of a

hemostatic plug Contributes to thrombin

formation

Page 8: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Biology of Hemostasis

VC + platelet plug formation = PRIMARY HEMOSTASIS Reversible Not associated with secretion

Page 9: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Biology of Hemostasis

Page 10: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Biology of Hemostasis

Intrinsic Pathway All the components

leading to the fibrin clot formation are intrinsic to the circulating plasma

Elevated PTT associated with an abnormality in the intrinsic clotting pathway

Page 11: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Biology of Hemostasis

Extrinsic Pathway Requires exposure of

tissue factor on the surface of the injured vessel wall

Starts with Factor VII

Abnormality of the extrinsic pathway is associated with an elevated PT

Page 12: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Biology of Hemostasis

Page 13: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Biology of Hemostasis

Fibrinolysis = lysis of the fibrin clot Plasminogen Plasmin degrades fibrin, Factor V and VIII

Plasminogenplasmin by several activators—tPA, (kalikrein increases release of tPA), uPA, factor XII

Plasminogen levels rise due to exercise, venous occlusion, and anoxia Breakdown of the clot permits restoration of blood flow and fibrin clot in

vessel wall may be replaced with collagen

Antithrombin III Binds and inhibits thrombin and factors IX, X, XI

Protein C Vitamin K-dependent Degrades fibrinogen and factors V and VIII

Protein S Vitamin K-dependent Protein C cofactor

Page 14: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Biology of Hemostasis

How do SCDs work?

The squeeze stimulates the release of tPA from the endothelial cells of vessels. Induction of fibrinolysis. (tPA is selective for fibrin-bound plasminogen

and converts to plasmin; therefore, fibrinolysis occurs mostly at the site of clot formation.)

Page 15: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Name that movie

Page 16: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Congenital Hemostatic Defects

Coagulation Factor Deficiencies Hemophilia

Factor VIII deficiency = Hemophilia A Sex-linked recessive Both prolonged aPTT and PT Need level to be 100% pre-op and 30% post-op Crosses placenta Hemophiliac Joint

No aspiration; ice; ROM exercises, factor VIII concentrate or cryoprecipitate

Factor IX deficiency = Hemophilia B/Christmas Disease Sex-linked recessive Need level 50% pre-operatively Prolonged aPTT and normal PT Tx-factor IX concentrate or cryoprecipitate

Page 17: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Congenital Hemostatic Defects

von Willibrand’s Disease MOST COMMON congenital bleeding disorder Low levels of vWFvariable decrease in Factor VIII due to

loss of the carrier protein vWF is necessary for normal platelet aggregation;

therefore deficiency presents in a similar fashion to platelet disorders

Prolonged bleeding time, possible abnormal PTT, normal PT

Types- I-partial quantitative deficiency (AD) II-qualitative defect (AD) III-total deficiency (AR)

Tx—intermediate purity factor VIII or DDAVP (Type I or II only)

Page 18: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Congenital Hemostatic Defects

Platelet disorders Glanzmann’s thrombocytopenia—deficiency in

GIIbIIIa receptor of platelets; therefore, platelets cannot bind to each other Tx-platelets

Bernard Soulier—Gp1b receptor deficiency; therefore, platelets cannot bind collagen via vWF Tx-platelets

Page 19: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Name that movie

Page 20: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Acquired Hemostatic Defects

Anticoagulation Heparin—potentiates ATIII action

Reversed with administration of protamine (1mg protamine for every 100u heparin received)

Follow aPTTwant 1.5-2.5x upper limit of nl (60-90) Does not cross placental barrier

Lovenox—potentiates ATIII and inhibits both thrombin and Factor Xa “more reliable therapeutic anticoagulation can be achieved” Drug effect can be determined by anti-Xa assay No definitive reversal

Warfarin (Coumadin) Inhibits Vitamin K synthesis Reversed by FFP or Vitamin K administration Follow INR/PT

Page 21: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Acquired Hemostatic Defects

Why do we bridge with heparin or Lovenox when initially starting Coumadin?

Protein C and S are inhibited before factors II, VII, IX and X which makes the patient relatively hypercoaguable for 5-7 days

Page 22: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Acquired Hemostatic Defects

Antiplatelet Medications Asprin—Platelet cyclooxygenase is irreversibly

inhibited ; decreases TXA2 which promotes platelet aggregation

Plavix (Clopidogrel)—ADP receptor antagonist Pentoxifylline—inhibits platelet aggregation and

decreases viscosity of blood; used in treatment of peripheral arterial disease

Page 23: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Acquired Hemostatic Defects

Heparin Induced Thrombocytopenia 2/2 antiplatelet Ab (IgG) that results in platelet

destruction Platelet count falls to <100K or by <50% in 5-7

days if first exposure or in 1-2 days if re-exposure

High incidence of platelet aggregation and thrombosis (white clot)

If suspected— STOP heparin Start alternate anticoagulation (lepirudin or

argatroban)

Page 24: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Acquired Hemostatic Defects

Disseminated Intravascular Coagulation Systemic process producing both thrombosis and

hemorrhage Exposure of blood to procoagulants Formation of fibrin in the circulation Fibrinolysis Depletion of clotting factors end-organ damage

Dx= decreased platelets, prolonged PT and aPTT, low fibrinogen, high fibrin split products, high D-dimer

Treat the underlying disease (sepsis, trauma, burns, malignancy)

Page 25: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Acquired Hemostatic Defects

Thrombocytopenia MOST COMMON abnormality of hemostasis Variety of etiologies (ITP, TTP, HUS, SLE,

lymphoma, secondary hypersplenism, portal HTN, uremia…)

In setting of massive transfusion—exchange of 1L of blood volume (~11units) decreases platelet count from 250K to 80K. Associated impaired ADP-stimulated aggregation if >10units of blood transfused.

Page 26: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Name that movie

Page 27: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Hypercoagulable States

Factor V Leiden Deficiency MOST COMMON congenital hypercoagulable

disorder AD Leiden variant of Factor V cannot be inactivated

by Protein C Increased risk for DVT, spontaneous abortion Tx = heparin or warfarin

Page 28: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Hypercoagulable States

AT-III deficiency Spontaneous venous thrombosis Heparin does not work on these patients unless

pretreated by FFP Tx: AT-III concentrated

Antiphospholipid Antibody Syndrome Presence of lupus anticoagulant that bind to

phospholipids and proteins on the cell membrane an interfere with clotting; HOWEVER, associated with thrombosis and habitual abortions (prolonged PTT in the face of a hypercoagulable state)

Tx: Heparin, coumadin

Page 29: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Hypercoagulable States

Amicar Aminocaproic acid Inhibits fibrinolysis by inhibiting plasmin Indications: DIC, persistent bleeding following

CPB, thrombolytic overdose

Aprotinin Inhibits fibrinolysis by inhibiting activation of

plasminogen to plasmin

Page 30: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Name that movie

Page 31: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Venous thromboembolism

DVT and PE Virchow’s triad = stasis, endothelial injury,

hypercoagulability Treatment for DVT

1st= warfarin x 6months 2nd= warfarin x 1year 3rd or significant PE = lifetime warfarin

Greenfield filters For patients with contraindications to anticoagulation Documented PE while on anticoagulation Free-floating iliofemoral clot IVC or femoral DVT Patients who have undergone previous pulmonary

embolectomy PE most commonly caused by DVT in iliofemoral region

Page 32: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Name that movie

Page 33: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Transfusion

PRBCs 1unit=~250mL Storage life ~35days 1unit increases Hgb by 1 and Hct by 3 Fever without hemolysis is the most common

transfusion reaction (1 in 6,000) Usually recipient antibody reaction against WBCs in

donor blood Acute Hemolytic reactions occur 1 in 35,000

Caused by ABO incompatibility or Ab mediated usually from human error (Ab in recipient binding to surface Ag on donor RBC)

Sx=hypotension, fever, dyspnea, chest pain, low back pain

Tx=fluids, diuretics, HCO3, histamine blockers, pressors

Page 34: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Transfusion

Platelets 50-100 billion in 50mL plasma Can be stored for ~7 days (viability declines after 3

days) Each platelet concentration should raise circulating

platelets by >5,000 (4-6 pack of platelets shound increase platelets by 20-30K)

Febrile nonhemolytic reactions more common than with PRBCs (incidence is ~30%)

Antiplatelet antibodies develop in 20% of patients after 10-20 transfusions

Indictions in active bleeding: plt<50K or plt<100K in setting of ICH; trauma victims who have received multiple transfusion

Contraindicated in HIT and TTP

Page 35: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Transfusion

FFP ~250 mL collected from 1 unit whole blood by

apheresis Stored between -18 and -30 degree C and is good

for 1 year Dose is ~10-15mL/kg Contains all coagulation factors, protein C, protein

S, and AT-III (only blood product with factor V) Indications-warfarin overdose, liver failure,

dilutional coagulopathy associated with massive transfusion

Highest risk of TRALI—important to distinguish from volume overload. Tx=supportive

Page 36: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Name that movie

Page 37: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Evaluation of the Surgical Patient at Hemostatic Risk

Preoperative Assessment History

Bruises without apparent injury Prolonged bleeding after injury PMHx—liver disease, congenital or acquired bleeding

disorders Medications

Labs—CBC, Coagulation panel, T&S or T&C

Intraoperative and Postoperative Ineffective local hemostasis Complications of blood transfusion Consumptive coagulopathy Fibrinolysis

Page 38: Hemostasis Shaina Eckhouse 10/12/2010. Objectives Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States

Questions?