2. Bleeding Flashcards
DIC.
a) Pathophysiology
b) Causes (CLOTS)
c) Clinical features
d) Confirming diagnosis (2 up, 2 down: 2 required)
e) Management
a) Dysregulation of both the clotting and lysis systems: evidence of both thrombin and plasmin activation
b) CLOTS: Cancer, Liver disease, Obstetric complications (HELLP, abruption, amniotic fluid embolism), Trauma, Sepsis (no.1)
c) - Bleeding from at least three unrelated sites:
e. g. ENT, GI tract, respiratory tract, site of venepuncture or IV infusion.
- Skin: petechiae, purpura, necrosis
- Systemic: fever, confusion, shock
- May be evidence of thrombosis (but bleeding usually predominates due to exhaustion of coagulation factors)
d) 2 out of: Low fibrinogen, low platelets, raised D-dimer, prolonged PT
e) - Treat underlying condition
- Transfusion of plasma (FFP) and platelets
- If thrombosis predominates: heparin
Major haemorrhage: management
a) Initial management
b) Blood transfusions/ other management
a) Identify major haemorrhage and perform A-E:
- c: stop catastrophic haemorrhage (direct pressure, pelvic binders and torniquets) + IV TxA
- A: secure, airway adjuncts, NG tube,
- B: oxygen 100%, SpO2 monitoring, RR
- C: HR and BP, 2x large-bore IV access (FBC, clotting, INR, group and save, cross-match), restricted volume IV fluids (to not exacerbate blood loss), initiate major haemorrhage protocol (call blood bank)
- D: GCS, pupils, glucose, neurology
- E: temperature, expose for sites of bleeding
b) - IV tranexamic acid (TxA)
- If anticoagulated - reversal (eg vitamin K) + prothrombin complex
- Initial transfusion with O-negative blood, FFP, cryoprecipitate and platelets
- Once cross-match complete - transfuse specific blood
- Imaging: FAST or XR/CT
- Definitive medical / vascular/ surgical management
Virchow’s triad for thrombosis
Stasis, endothelial injury, hypercoagulability
Coagulation cascade.
a) Intrinsic pathway - trigger? - measured via…? - affected by what diseases and drugs?
b) Extrinsic pathway - trigger? - measured via…? - affected by what diseases and drugs?
c) Final common pathway? - measured via…? - affected by what drugs?
d) How does dabigatran work?
e) How do the other DOACs work?
f) How does warfarin work?
g) How does heparin work?
a) Endothelial injury; APTT; prolonged by haemophilia A and B, vWD, liver disease and heparIN
b) Tissue factor (in response to tissue injury); prothrombin time; prolonged by vitamin K deficiency, liver disease and warfarin
(WEPT; Warfarin, Extrinsic, Prothrombin Time)
c) Factor X > Factor Xa (which converts prothrombin > thrombin; thrombin converts fibrinogen > fibrin)
- measured via PT (as for extrinsic pathway)
- RivaroXaban, apiXaban
d) Direct thrombin inhibitor (D for direct)
e) - Indirect thrombin inhibitor: through inhibiting the conversion of factor X to Xa
f) Vit K antagonist (stops profuction of factor II, VII, IX and X)
g) Indirect thrombin inhibitor: through activation of antithrombin
Bleeding disorders.
a) Congenital - 2 main causes
b) Acquired - pathogenesis and main causes
a) - vWD: auto-dominant, muco-cutaneous bleeding
- Haemophilia: XLR (boys), haemarthrosis, affects intrinsic pathway (i.e. increased APTT)
b) - Coagulation factors: liver disease, haemophilia, DIC
- Platelets: thrombocytopenia, antiplatelets, platelet dysfunction, malignancy, ITP, renal failure
- Vitamin K: deficiency, warfarin
Coagulation disorders vs. platelet disorders
- bleeding types
- Coagulation disorders: haemarthrosis, intramuscular bleeding, haematuria
- Platelet disorders: profuse bleeding from cuts, gum bleeding (eg post-tooth extraction), epistaxis, GI bleeding, intraoperative bleeding, menorrhagia
Spot the bleeding disorder.
a) Normal platelet count, normal PT, raised APTT, normal bleeding time, deficient factor VIII
b) Normal platelet count, normal PT, raised APTT, normal bleeding time, deficient factor IX
c) Normal platelet count, normal PT, raised APTT, prolonged bleeding time, impaired platelet aggregation, reduced activity of factor XIII
d) Thrombocytopenia, prolonged PT, prolonged APTT, deficiency of all coagulation factors - 2 DDx - further tests to distinguish them?
e) Normal platelet count, APPT > PT; pre-operative
f) Normal platelet count, PT > APTT; metallic heart valve
a) Haemophilia A: factor VIII
b) Haemophilia B: factor IX
c) von Willebrand’s disease (vWD)
d) DIC or liver disease:
- thrombocytopenia occurs in liver disease due to reduced TPO production in the liver and hence reduced thrombopoesis)
- in DIC you have the “2 up/ 2 down” - raised PT, raised D-dimer; low platelets, low fibrinogen
e) Heparin
f) Warfarin
Haemophilia.
a) Pathogenesis
b) Presentation
c) Investigations
d) Management
a) A (factor VIII deficiency) and B (factor IX): both are XLR
b) Spontaneous haemarthrosis (pathognomonic - may cause arthropathy), intramuscular bleeding (may cause compartment syndrome), haematuria, IC bleeds
c) - FBC - may have low Hb and haematocrit if recent bleed; normal platelets
- Bleeding studies: PT, bleeding time, fibrinogen levels and von Willebrand factor all normal
- APTT usually raised
- MRI affected joints/muscles
d) - Bleeding prophylaxis with factor VIII / IX infusions (three times per week)
- Acute bleeding: FFP + factor VIII / IX
- Surveillance for joint health
von Willebrand’s disease (vWD).
a) Functions of vWF (2)
b) Causes
c) Presentation
d) Investigations
e) Management
a) Platelet aggregation and binding of factor VIII to prevent its clearance
b) Most are inherited: autosomal dominant (3 types); more rarely acquired
c) Mucocutaneous bleeding: epistaxis, menorrhagia, bleeding gums, profuse bleeding from cuts/ during surgery, possibly GI bleeds
d) - FBC: Hb and haematocrit may be low if recent bleed; platelet count normal
- Bleeding studies: PT and fibrinogen normal; raised APTT and bleeding time; deficiency of vWF +/- factor VIII
e) - Avoid antiplatelets and NSAIDs
- If severe: prophylaxis with vWF infusions
- In acute bleed: TxA and desmopressin (increases activity of vWF and factor VIII) + infusions of vWF/ factor VIII
- Menorrhagia: COCP/ IUS
Platelet disorders: causes
a) Impaired production (thrombocytopenic)
b) Decreased survival (thrombocytopenic)
c) Impaired function (non-thrombocytopenic)
a) - Congenital: Fanconi’s anaemia, WAS
- Acquired: viral infections (EBV, HIV, hepatitis), bone marrow failure (leukaemia, aplastic anaemia), liver failure
b) Auto-immune (ITP, connective tissue disease), drug-induced (heparin, aspirin, NSAIDs), hypersplenism, HELLP syndrome, DIC
c) vWD, CKD, paraproteinaemia (eg. myeloma)
Platelet disorder: assessment and management
a) Common presentation
b) Urgent referral criteria
c) Other red flags
d) Investigations
e) Management
a) Petechiae/purpura, profuse bleeding from cuts, bleeding gums, epistaxis, menorrhagia, GI bleeds, bleeding on NSAIDs/aspirin, incidental findings
b) Severe thrombocytopenia (< 20), severe bleeding, blast cells on blood film
c) Fever, night sweats, lympadenopathy, weight loss, hepato/splenomegaly, pancytopenia
d) - FBC, clotting (PT, APTT, fibrinogen, D-dimer)
- Other bleeding tests (bleeding time, vWF)
e) - May need platelet transfusions
- May require blood transfusions
- Acutely, may also respond to TxA and desmopressin
(note: in general, don’t use TxA in DIC as the excess fibrin DOES need to be broke down)
Tranexamic acid.
a) How does it work?
b) When is it indicated?
c) How can it be given?
d) When is it contraindicated?
a) Anti-fibrinolytic
b) - Prevention and Rx of major haemorrhage (eg. trauma, surgery, obstetric)
- Menorrhagia, Epistaxis, Other bleeding
- Hereditary angio-oedema
c) Oral, IV, SC
d) DIC (unless predominant activation of fibrinolytic system with severe bleeding); other VTE
Immune thrombocytopenic purpura (ITP)
a) Pathogenesis and causes
b) Diagnostic criteria
c) Presentation
d) Investigations
e) Management
a) Auto-immune destruction of platelets; usually idiopathic (primary) but may be secondary (eg. SLE/APLS, drug-induced, viral infection)
- May be post-viral infection in children
b) Platelet count <100 in the absence of other causes
c) Ranges from: asymptomatic, petechiae/bruising, nosebleeds/menorrhagia, GI bleeds/haematuria, to severe IC bleeds (possibly fatal)
d) - FBC: isolated thrombocytopenia
- May do blood film if worried about leukaemia/ other sinister cause
e) - Conservative (usually sufficient): avoid NSAIDs, avoid contact sports, monitor symptoms +/- FBC
- If symptomatic: medication
- 1st line: prednisolone, IVIG
- 2nd line: rituximab, high-dose dexamethasone
- Menorrhagia: TxA, COCP/IUS
- Platelet transfusions and splenectomy rarely
Thrombotic thrombocytopenic purpura.
- Response to infection, trauma or heparin
- Causes bleeding + thrombosis
- Neurological symptoms common
- Treatment supportive (may include steroids/ plasmapheresis)
- Mortality high
Transfusion reactions.
a) Instant haemolytic reaction
b) Fever, rigors and haemolysis a few days post-transfusion
c) Rapid onset of SOB, hypoxia and bilateral pulmonary infiltrates on XR within 6 hours of transfusion
a) ABO incompatibility
b) Delayed haemolytic reaction
c) Transfusion-associated acute lung injury (TRALI)
