Phys · haematological
Coagulation Disorders — Bleeding, Thrombosis and the Abnormal Coagulation Screen
Also known as coagulopathy · bleeding disorder · abnormal coagulation screen · prolonged aPTT · prolonged PT · elevated INR · haemophilia A · haemophilia B · Christmas disease · factor VIII deficiency · factor IX deficiency · von Willebrand disease · vWD · disseminated intravascular coagulation · DIC · antiphospholipid syndrome · APS · lupus anticoagulant · immune thrombocytopenia · ITP · heparin-induced thrombocytopenia · HIT · thrombotic thrombocytopenic purpura · TTP · mixing study · emicizumab · desmopressin · DDAVP
Consultant-physician-depth guide to coagulation disorders for FRACP DWE and DCE. Covers the coagulation cascade (intrinsic, extrinsic, common pathways), inherited bleeding disorders (haemophilia A, haemophilia B, von Willebrand disease), acquired coagulopathies (DIC, liver disease, warfarin, massive transfusion), antiphospholipid syndrome, thrombocytopenia (ITP, HIT, TTP/HUS), mixing study interpretation, and the systematic investigation of the abnormal coagulation screen.
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Red flags
- Intracranial haemorrhage in a patient with a bleeding disorder or severe thrombocytopenia — a medical emergency requiring immediate factor replacement or platelet transfusion
- Platelet count less than 10 x 10^9/L with bleeding, or less than 20 x 10^9/L with fever or sepsis — assess for urgent platelet transfusion
- DIC with fibrinogen less than 1.0 g/L and active bleeding — give cryoprecipitate urgently; do not wait for repeat labs
- Suspected HIT with new thrombosis and falling platelets — stop ALL heparin immediately and start a non-heparin anticoagulant; do not wait for confirmatory testing
- TTP suspected (thrombocytopenia plus microangiopathic haemolytic anaemia plus neurologic or renal involvement) — initiate plasma exchange within hours; untreated mortality approaches 90 per cent
- Catastrophic antiphospholipid syndrome (multi-organ thrombosis over days) — ICU-level care with triple therapy (anticoagulation, corticosteroids, plasma exchange); mortality 30-50 per cent
- Haemophilia with a new severe headache, confusion, or focal neurology — treat as intracranial haemorrhage until proven otherwise; give factor immediately before imaging
Coagulation Disorders — Bleeding, Thrombosis and the Abnormal Coagulation Screen
The answer first
Coagulation disorders fall into three clinical questions the examiner asks: Is the patient bleeding, clotting, or does the lab look odd? The registrar who answers all three will pass this station. The one who chases a single prolonged clotting time without asking whether the patient is bleeding or thrombosing will fail it. [1]
The framework is built on three axes: [1]
- Platelets versus coagulation factors. Platelet bleeding is mucocutaneous — petechiae, epistaxis, menorrhagia, GI bleeding. Factor bleeding is deep — haemarthrosis, muscle bleeds, intracranial. The platelet count and the coagulation screen split these two worlds.
- Bleeding versus thrombosis. A prolonged aPTT from haemophilia causes bleeding. A prolonged aPTT from a lupus anticoagulant paradoxically causes thrombosis. The mixing study separates these. Never assume a prolonged clotting time means a bleeding tendency.
- Inherited versus acquired. A lifelong history of post-surgical or dental bleeding points to haemophilia or von Willebrand disease. A new coagulopathy in a sick patient points to DIC, liver disease, or warfarin. [1]
The single most tested principle for the exam: the mixing study is the gateway to the abnormal coagulation screen. Mix the patient's plasma with normal pooled plasma. If the prolonged clotting time corrects, a factor deficiency is present. If it does not correct, an inhibitor is present — and the next question is whether that inhibitor causes bleeding (a factor inhibitor, like a haemophilia inhibitor) or thrombosis (a lupus anticoagulant). [1]
References12ShowHide
- [1]Mannucci PM, Tuddenham EG The hemophilias--from royal genes to gene therapy N Engl J Med, 2001.PMID 11396445
- [2]Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab Prophylaxis in Hemophilia A with Inhibitors N Engl J Med, 2017.PMID 28691557
- [3]Leebeek FWG, Eikenboom JCJ Von Willebrand's Disease N Engl J Med, 2016.PMID 27959741
- [4]Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation Thromb Haemost, 2001.PMID 11816725
- [5]Tripodi A, Mannucci PM The coagulopathy of chronic liver disease N Engl J Med, 2011.PMID 21751907
- [6]Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) J Thromb Haemost, 2006.PMID 16420554
- [7]Giannakopoulos B, Krilis SA The pathogenesis of the antiphospholipid syndrome N Engl J Med, 2013.PMID 23484830
- [8]Cervera R Update on the diagnosis, treatment, and prognosis of the catastrophic antiphospholipid syndrome Curr Rheumatol Rep, 2010.PMID 20425537
- [9]Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia Blood Adv, 2019.PMID 31794604
- [10]Cuker A, Gimotty PA, Crowther MA, Warkentin TE Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis Blood, 2012.PMID 22990018
- [11]Warkentin TE Heparin-induced thrombocytopenia: diagnosis and management Circulation, 2004.PMID 15520327
- [12]Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura N Engl J Med, 2019.PMID 30625070