You are on page 1of 4

Hemostasis Disorders

There is normal anticoagulation in small blood vessels:


Heparin-like molecules: enhance Antithrombin III activity. Prostaglandin I2 activated. Protein C and S activated. Tissue Plasminogen Activator activated.

Procoagulants released in small vessel injury:


Thromboxane A2: conversion of prostaglandin I2 to Thromboxane A2 by Thromboxane synthase. Von Willebrand Factor: platelet adhesion molecule. Factor VIII:C. Tissue thromboplastin (factor III).

Receptors for chemicals released by platelets:


Von Willebrand Factor: GpIb.

Fibrinogen:
GpIIb:IIIa; inhibited by ticlopidine and clopidogrel and abciximab.

Coagulation system:
Extrinsic vs intrinsic.

Coagulation pathway: Extrinsic vs Intrinsic:

Vitamin K-dependent factors:


Factors II, VII, IX, X; proteins C and S. Warfarin, an anticoagulant, inhibits vitamin K activity.

Fibrinolytic system:
Activation by tPA; release of plasmin.

Thrombolytic therapy:
Alteplace + reteplase (forms of tPA).

Activators of plasminogen:
Factor XIIa, streptokinase, anistreplase, urokinase.

Small vessel hemostasis response to injury:


Vascular:
Vasoconstriction after injury.

Platelet:
Platelet adhesion; release reaction; platelet plug.

Coagulation:
Thrombin production.

Fibrinolytic:
Fibrin monomers cleaved by plasmin.

Tests:
Ristocetin cofactor assay: vWF test. Platelet aggregation test: platelets. Prothrombin time: tests VII, X, V, II, I; inhibited by warfarin; 11-15 seconds. Partial thromboplastin time: tests XII, XI, IX, VIII, X, V, II, I; inhibited by heparin; 25-40 seconds. Fibrinogen degradation products: detect plasmin activity. d-Dimer assay: detects fibrin in fibrin clots.

Platelet disorders:
Thrombocytopenia:
Decreased platelet count. Decreased production (anemia, leukemia) or increased destruction (idiopathic thrombocytopenic purpura, drugs; thrombotic thrombocytopenic purpura).

Yhrombocytosis:
Increased platelet count. Eg., essential thrombocytopenia, polycythemia vera. Eg., iron deficiency, infections, splenectomy, malignancy.

Findings:
Epistaxis, petechia, ecchymoses.

Coagulation disorders:
Decreased production; eg., hemophilia A, cirrhosis. Inhibition; antibodies against coagulation factors. Consumption; DIC.

Findings:
Late rebleeding; excessive bleeding.

Hemophilia A:
XR disorder. Deficient VIII:C. Bleeding problems. Treatment: desmopressin acetate.

Hemophilia B:
Christmas disease. Deficient factor IX.

Classic von Willebrand disease:


AD disorder. Deficient vWF and VIII:C. Easy bleeding. Increased PTT; normal PT. Treatment: desmopressin acetate, oral contraceptives.

Vitamin K deficiency:
Activates factors II, VII, IX, X, and proteins C and S.

Causes of deficiency:
Breast milk lacks vitamin K. Prolonged antibiotic treatment. Decreased bowel absorption of vitamin K. Decreased vitamin K activation by liver epoxidase reductase.

Findings:
GI bleeding, intracranial hemorrhage. Treatment: give vitamin K.

Disseminated intravascular coagulation:


Causes:
Sepsis; disseminated malignancy like cancer, etc.; crush injuries, rattlesnake venom. Activated coagulation cascade. Fibrin thrombin in circulation. Fibrinolytic system activation. Increased PT/PTT; decreased fibrinogen. Thrombocytopenia, increased bleeding time. Fibrinolysis abnormalities.

Treatment: treat underlying disease.

Primary fibrinolysis:
Causes:
Open heart surgery. Liver disease. Prostatectomy. Fibrin degradation products interfere with platelet aggregation. Severe bleeding. Increased PT/PTT.

Secondary fibrinolysis:
Compensatory reaction in presence of DIC.

Thrombosis syndromes: acquired thrombosis syndromes:


Antiphospholipid syndrome:
SLE, HIV. Antiphospholipid antibodies present. Arterial and venous thrombosis syndromes; repeated abortions; strokes; thromboembolisms.

Causes:
Folate / vitamin B12 deficiency, oral contraceptives, hyperviscosity.

Hereditary thrombosis syndromes:


AD syndromes. Deep venous thrombosis.

Factor V-Leiden:
Most common.

Antithrombin III deficiency:


Prolongation of PT and PTT.

Protein C and S deficiency:


Treatment: warfarin.