5. Bleeding disorders Flashcards
which tests are used to measure platelet no. and activity
platelet count and bleeding time
which parts of the clotting cascade do the APTT, PT and INR tests measure
APTT = intrinsic and common pathway
PT and INR (P’s PT/mean PT) = extrinsic pathway
which medication should be used to:
- treat arterial thrombi (eg unstable angina, MI)
- treat venous thrombi (eg DVT or PE)
- prophylaxis in AF, valvular heart disease, artificial heart valves or antiphospholipid syndrome
- anti-platelets: aspirin
- anti-coagulants: warfarin or heparin
- anti-coagulants: warfarin or heparin
describe the MOA of aspirin
Irreversibly inactivates platelet cyclooxygenase… suppresses production of thromboxane A2 (platelet aggregator)… inhibits platelet aggregation
describe the MOA of warfarin
Inhibits vitamin K epoxide reductase… no recycling of oxidised VitK… no activation of coagulation factors II, VII, IX and X.
describe the MOA of heparin
Enhances activity of anti-thrombin III… inactivates thrombin and factor X
what are the effects of aspirin, warfarin and heparin on coagulation tests
- aspirin: increased bleeding time (as measure of platelet activity)
- warfarin: increased PT and INR
- heparin: increased APTT
P presents with following lab tests:
- increased PT and INR
- increased APTT
- decreased fibrinogen
- increased fibrin degradation products
what is the likely diagnosis and why
Disseminated intravascular coagulation:
- fibrinogen consumed in microthrombi formation (decreased fibrinogen)… then broken down by fibrinolysis… release of fibrin degradation products, e.g. D-dimers
- run out of of coagulation factors, etc. (increased PT, INR and APTT)
describe the pathophysiology of DIC
Thrombohaemorrhagic disorder occurring as a secondary complication in a variety of disorders.
A clotting activator gets into blood and causes microthrombi formation throughout circulation… consumes platelets, fibrin and coagulation factors, and activates fibrinolysis… haemorrhage.
i) microthrombi formation… tissue ischaemia
ii) haemorrhage - can be severe, from mucous membranes and into skin/internal organs
iii) microangiopathic haemolytic anaemia - as RBCs squeeze through narrow vessels narrowed by microthrombi
name 5 different causes of DIC
- infection and sepsis - esp. by gram negative as GNB produce endotoxins that damage emdothelium and activate clotting
- severe trauma - esp. to brain as contains large amounts of thromboplastin (tissue factor), or extensive burns
- obstetric complications (50%) - e.g. amniotic fluid embolism (pro-coagulant), retained dead foetus (releases thromboplastin)
- malignancy (33%) - e.g. mucin-secreting adenocarcinoma: release mucin (pro-coagulant), produce inflammation and tissue damage
- snake bite
a P presents with:
- frequent mucosal bleeding, e.g. epistaxis, menorrhagia
- prolonged bleeding time
- prolonged APTT
what is the likely diagnosis
von Willebrand disease (most common inherited bleeding disorder)
- prolonged bleeding time as affects platelet aggregation
- prolonged APTT as affects F8, part of intrinsic pathway
describe the pathophysiology of vWB disease
Autosomal dominant inherited deficiency in von Willebrand factor.
Involves impaired platelet plug and fibrin clot formation and thus inefficient haemostasis, as vWF is a glycoprotein with 3 functions:
- platelet adhesion to vessel walls (vWF binds to collagen and platelets)
2. platelet aggregation
3. stability and transport of Factor VIII
a P presents with:
- petechiae
- low platelet count
- prolonged bleeding time
what is the likely diagnosis
thrombocytopenia = platelet count <100 x 10^9/L
describe different causes for thrombocytopenia
- decreased platelet production - due to BM infiltration by malignancy, cytotoxic drugs, infections (e.g. measles and HIV) or B12 and folate deficiency (required for platelet production)
- decreased platelet survival - due to immunologic destruction (eg ITP) or non-immunological destruction (eg DIC)
- platelet sequestration - due to hypersplenism
- dilutional - due to massive blood transfusions
a P presents with:
- prolonged APTT
- low F8 assay
what is the likely diagnosis and what are the associated symptoms
Haemophilia A (most common inherited disease associated with serious bleeding)
Signs and symptoms:
- easy bruising
- massive haemorrhage after trauma/surgery
- “spontaneous” haemorrhages in areas subject to minor trauma, e.g. joints - haemarthrosis
- joint deformities (due to recurrent haemarthrosis)
