Acquired bleeding disorders Flashcards
Clotting requires:
platelets; vessel wall; clotting factors
Prothrombin time (PT)
Measures factors II,V, VII, X, fibrinogen - extrinsic pathway
- Only test that measures FVII
- Time in seconds from exposure to clot formation
Causes of prolonged PT
Vitamin K deficiency
- Liver disease
- Massive blood transfusion due to dilution of clotting factors
Isolated prolonged PT along with normal APTT =
Early liver disease
- (factor 7 drops the quickest as shortest half-life)
-
Activated Partial Thromboplastin Time (APTT)
Measures other factors, not 7
- Kallikrein and HMWK and Factor XII are contact factors which can mess up APTT and make it look prolonged but deficiencies will not cause bleeding problems
Causes of prolonged APTT
- Deficiency or inhibition of factors + fibrinogen
- Liver disease, Warfarin, Haemophilia
Thrombin time
- Looking at function and amount of function
- Measures fibrinogen
Causes of prolonged TT
Dysfibrinogenaemia – no fibrinogen, Hypofibrinogenaemia – low fibrinogen, Hepatocellular disease, DIC, Heparin
Lupus anticoagulant (LAC)
- IgG/ IgM autoantibody – antiphospholipid antibody
- Interferes with APTT test in vitro and prolongs APTT
- Can do LAC screen
- In vivo more likely to have thrombosis than bleeding
Heparin
- Wraps around antithrombin
- Inhibits Factor X
- UFH = inhibits Factor Xa and Thrombin and switch off coagulation cascade
Unfractioned heparin monitoring (UFH)
- Badly monitored
- Half life - 45-90 mins
- Monitor with APTT
- Can be hard to anticoagulate some infants
Low molecular weight heparin
- More reliable that UFH, renally excreted so may not reach therapeutic range
- Monitor anti-Xa levels
HIT = heparin induced thrombocytopenia
Immune complex forms causing drop in platelet count
- Skin/allergic reactions and bleeding
Treatment of bleeding
- Patients on UFH - Stop IV heparin, administer protamine sulphate - potential allergy
- Patients on LMWH - Stop LMWH, Protamine reverses 60% of the effects
Warfarin
- prevents activation of vitamin K - Factors 2,7,9,10 are all vitamin K dependant
- Monitor treatment by INR
Treatment of bleeding or excessive anticoagulation on warfarin
- Stop warfarin
- Give prothrombin complex concentration
- Vit K IV
- Measure INR 15 mins and 12 hours after PCC
Fondaparinux
- Alternative to heparin – similar action
- Indirect anti-Xa activity
- Half-life of 17-20 hours
- No specific antidote
- Bleeding – stop treatment and general haemoastatic measures
- If critical bleeding – consider FVIIa
Aspirin
- Anti-platelet agent
- Inactivates platelet cyclooxygenase
- Give 2-3 doses of platelets in critical bleeding
Bleeding in vitamin K deficiency
- Deficiencies of factors II, VII, IX and X
- Treatment with IV/oral vitamin K
- Causes = obstructive jaundice, nutrition deficiency
Bleeding in liver disease
- Aka cirrhotic coagulopathy
- Reduced plasma concentration of coag factors except FVIII
- Treated with platelet transfusions, FFP or prothrombin complex concentrate
Bleeding in renal disease
Causes:
- Anaemia - RBC’s are needed for platelet function (release ADP)
- Uraemia - Disrupts platelet-platelet and platelet-vessel wall interactions
Prevention of bleeding
- Correct anaemia - EPO and transfusions
DDAVP - Desmopressin - stimulates release of vWF - Tranexamic acid
Haemostatic abnormalities in massive transfusion
- dilutional depletion of platelets and coagulation factors
- Acidosis
- Hypothermia
- Haemorrhages can cause DIC
DIC = disseminated intravascular coagulation
- Characterised by systemic activation of pathways leading to and regulating coagulation, which can result in generation of fibrin clots that may cause organ failure with concomitant consumption of platelets and coagulation factors that may result in clinical bleeding
DIC pathogenesis
oExcess thrombin generation Microvascular thrombosis – tissue ischaemia and organ damage oReduced natural anticoagulant activity oDecreased fibrinolysis Aetiology
Causes of DIC
- Sepsis
- Trauma
- Acute intravascular haemolysis
- Liver disease
- Chronic causes = malignancy
Diagnosis and management of DIC
- Diagnosed via presence of underlying disorder, Global coagulation tests - Low platelet count, elevated D-dimer, prolonged PT, low fibrinogen
- Treat underlying cause - antibiotics, Vit K supplementation