L28 – Inherited & Acquired Bleeding Disorders Flashcards
List the endothelial factors that inhibit blood coagulation?
Antithrombin, tissue factor pathway inhibitor, protein S, protein C, Thrombomodulin
List endothelial factors that cause vasodilation and inhibit platelet aggregation?
Prostacyclin, nitric oxide
List endothelial factors that initiate coagulation?
- Von Willebrand factor
- Tissue factor (rich in thromboplastin, can be used to check prothrombin time (PT))
List 4 functions of platelets in forming blood clot?
Form a primary plug to close vascular defect (+ve feedback)
Release serotonin, thromboxane = stimulate vascular constriction
Release ADP, TXA2 for platelet aggregation
Provide a pro-coagulant surface for coagulation reactions to generate fibrin clot
Which coagulants are produced by the liver?
All except VWF, Factor VIII
2 functions of Von Willebrand factor (VWF)?
Bridges between platelet and collagen in platelet adhesion
Carrier protein = protects factor VIII from degradation in circulation
Describe the structure involved in platelet to platelet adhesion?
- Glycoprotein IIb/IIIa complex bind plt together
List the coagulation factors with longest and shortest t1/2
Longest = Factor 1
Shortest = factor 7
Thrombin activates which coagulation factors to form a positive feedback loop?
Factor 5,8,11
What is the convergence point of the intrinsic and extrinsic pathway for clot?
Extrinsic and intrinsic pathways converge at Factor X
What is the end product of the final common coagulation pathway
Fibrin
3 principle mechanisms of bleeding disorders?
- Defective blood vessel
- Defective Platelets
- Defective coagulation factors and VWF
Define the 2 patterns of bleeding?
Platelet/vessel type: Mucocutaneous bleeding*
Coagulation type: Delayed bleeding, Deep-seated bleeding*
Give examples of mucocutaneous and deep-seated bleeding?
Muco = petechiae & bruises, gum bleeding, menorrhagia, retinal hemorrhage
Deep-seated = joint (haemarthrosis), soft tissue (muscle haematoma)
What is the most important prelim. evaluation of bleeding disorder?
Bleeding history
- Age of onset of bleeding disorder
- Severity and progression
- Family members affected?
Acquired bleeding disorders are more common than inherited. T or F?
True
List some types of drugs that can cause bleeding disorders.
- Oral anticoagulants
- Anti-platelet drugs
- Chemotherapy
List the 3 functional tests for coagulation factors.
- Prothrombin time (PT)
- Activated partial thromboplastin time (APTT)
- Thrombin time (TT)
Define what is tested in PT?
Extrinsic pathway = factor 7
Common pathway = factor 10 ,factor 5, prothrombin (F2), Fibrinogen (F1)
What defect is indicated in Isolated Prolonged PT?
How about concurrent APTT prolong?
isolated = factor VII deficiency
PT + APTT prolonged = intrinsic/ final common pathway defects
List 3 common causes of prolonged PT?
Vitamin K deficiency
Vitamin K antagonists (e.g. warfarin)
liver disease
Define what is tested in APTT?
intrinsic pathway = Factor 12,11,9,8
final common pathway = 10,5, prothrombin, fibrinogen
What defects are indicated in isolated prolonged APTT?
- Intrinsic pathway: Deficiencies of Factor 8,9,11,12
- Inhibitors of factor 8 or others or lupus anticoagulant
- Contact factor def. ((Pre)Kallikrein, Factor 12, HMWK)
- Unfractionated/ contam. heparin
Define what is tested in Thrombin Time?
evaluates fibrinogen
What defects are indicated in prolonged TT?
Low fibrinogen:
1) Deficiency / dysfunction of fibrinogen (hypofibrinogenemia / afibrinogenaemia/ dysfibrinogenemia)
2) Inhibition of thrombin by heparin (e.g. contamination)
3) DIC consuming clotting factors
4) Liver disease = defect synthesis of fibrinogen
List some causes of Increased fibrinogen levels?
- Hormone-related: female sex, pregnancy, oral contraception
- Acute phase reaction (e.g. infection, lupus)
Difference in the initiation of clotting in vitro and in vivo?
In vitro = need contact factors like Prekallikrein to start
In vivo = need tissue factor and platelets to start
Describe the ddx of prolonged APTT?
What type of bleeding is asso. with platelet disorders
Mucocutaneous bleeding
List 3 causes of thrombocytopenia?
- Decreased platelet production from the marrow: e.g. due to malignancies
- Increased consumption of platelets (immune and non-immune causes)
- Others: Abnormal pooling in spleen, or dilutional (e.g. massive blood transfusion).
Does drug-induced platelet disorder create functional or numerical disorder?
Functional
List 3 tests to assess platelet disorders
- CBC platelet count
- PBS morphology
- Platelet function test: aggregometry that measures aggregation response of the platelets to different agonists
Indication for platelet function test?
if normal platelet count, normal PT and APTT, but mucocutaneous bleeding persists
