Module 24 · GI, liver & haematology

Haematology, coagulation and transfusion

NewPhase 2

Haematology for the ICU: restrictive transfusion and reactions, anticoagulant reversal, DIC and sepsis-induced coagulopathy, HIT, TTP/TMA, and ICU thrombocytopenia with viscoelastic-guided therapy.

6 topics

Drugs in this module

Doses written for this module's context. The same drug may read differently in another module.

Packed red blood cells

Blood product

Indications
Anaemia below transfusion threshold; haemorrhage
Adult dose
1 unit at a time in non-bleeding patients, then reassess Hb (each unit raises Hb ~1 g/dL in a 70 kg adult).
Preparation (India)
Indian PRBC unit ~250-350 mL (from 350 or 450 mL donation).

Platelet concentrate

Blood product

Indications
Thrombocytopenia with bleeding or below prophylactic threshold
Adult dose
1 apheresis (single-donor) unit or 4-6 random-donor units (1 unit/10 kg); expected rise 30-50 × 10⁹/L per apheresis unit.
Preparation (India)
Random-donor ~50-60 mL each; single-donor apheresis ~200-300 mL.

Fresh frozen plasma

Blood product

Indications
Bleeding with coagulation factor deficiency; TTP if plasma exchange delayed; warfarin reversal if PCC unavailable
Adult dose
15-20 mL/kg (about 4-5 units of ~200-250 mL in 70 kg).
Cautions
TACO, TRALI, allergic reactions; slow to thaw (20-30 min).

Four-factor prothrombin complex concentrate

Coagulation factor concentrate

Indications
Warfarin reversal in major bleeding; factor Xa inhibitor bleeding when andexanet unavailable
Adult dose
Warfarin: INR 2-4 25 units/kg, 4-6 35 units/kg, > 6 50 units/kg (max 5,000 units), or fixed 1,000-1,500 units. Xa inhibitor: 50 units/kg (or 2,000 units).
Preparation (India)
500 or 600 unit vials (factor IX units); reconstitute with supplied water.
Cautions
Thrombosis risk; always give with vitamin K for warfarin.

Vitamin K1 (phytomenadione)

Vitamin

Indications
Warfarin reversal
Adult dose
Major bleeding: 5-10 mg slow IV (with PCC). INR > 10 without bleeding: 2.5-5 mg oral.
Cautions
Slow IV over 20-30 min (anaphylactoid reactions).

Idarucizumab

Monoclonal antibody fragment

Indications
Dabigatran reversal for life-threatening bleeding or urgent surgery
Adult dose
5 g IV (two 2.5 g vials consecutively).

Protamine sulfate

Heparin antagonist

Indications
Heparin/LMWH reversal
Adult dose
UFH: 1 mg per 100 units given in previous 2-3 h (max 50 mg). Enoxaparin: 1 mg per 1 mg enoxaparin if within 8 h (0.5 mg per mg if 8-12 h); partial reversal only.
Preparation (India)
10 mg/mL; give slowly ≤ 5 mg/min.
Cautions
Hypotension, anaphylaxis, pulmonary hypertension (fish allergy, prior protamine insulin, vasectomy).

Desmopressin (DDAVP)

Vasopressin analogue

Indications
Antiplatelet-associated or uraemic platelet dysfunction with bleeding
Adult dose
0.3 mcg/kg IV in 50 mL NS over 30 min (single dose).
Cautions
Hyponatraemia (restrict free water), tachyphylaxis after repeated doses.

Argatroban

Direct thrombin inhibitor

Indications
Heparin-induced thrombocytopenia
Adult dose
2 mcg/kg/min IV (0.5-1.2 mcg/kg/min in heart failure, multi-organ failure, hepatic dysfunction or post-cardiac surgery); titrate to aPTT 1.5-3 times baseline.
Preparation (India)
250 mg/2.5 mL; 250 mg in 250 mL NS = 1 mg/mL.
Cautions
Hepatic clearance; prolongs INR (complicates warfarin overlap).

Fondaparinux

Factor Xa inhibitor (indirect)

Indications
HIT (stable patients, adequate renal function)
Adult dose
Weight < 50 kg 5 mg, 50-100 kg 7.5 mg, > 100 kg 10 mg SC once daily.
Renal / hepatic
Avoid if CrCl < 30 mL/min.

Methylprednisolone

Corticosteroid

Indications
Immune TTP
Adult dose
1 g IV daily for 3 days (or prednisolone 1 mg/kg/day).

Rituximab

Anti-CD20 monoclonal antibody

Indications
Immune TTP
Adult dose
375 mg/m² IV weekly for 4 doses.
Cautions
Infusion reactions; HBV reactivation (screen HBsAg/anti-HBc).

Caplacizumab

Anti-vWF nanobody

Indications
Immune TTP (with TPE and immunosuppression)
Adult dose
10 mg IV before first TPE, then 10 mg SC daily during TPE and for 30 days after.
Cautions
Bleeding (mucocutaneous).

Cryoprecipitate

Blood product

Indications
Fibrinogen < 150 mg/dL with bleeding (< 100 in DIC without bleeding is not an indication alone)
Adult dose
1 unit/10 kg (about 8-10 units) raises fibrinogen ~50-100 mg/dL.

Tranexamic acid

Antifibrinolytic

Indications
Hyperfibrinolysis; trauma and PPH (see those modules)
Adult dose
1 g IV over 10 min, then 1 g over 8 h (trauma); in hyperfibrinolysis on viscoelastic testing 1 g IV.
Renal / hepatic
Reduce in renal failure (seizure risk).

Module references (19)

  1. 1

    Rossaint R, Afshari A, Bouillon B, et al. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Crit Care 2023;27:80.

  2. 2

    CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2). Lancet 2010;376:23-32.

  3. 3

    Vlaar APJ, Dionne JC, de Bruin S, et al. Transfusion strategies in bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine. Intensive Care Med 2021;47:1368-92.

  4. 4

    Carson JL, Stanworth SJ, Guyatt G, et al. Red blood cell transfusion: 2023 AABB international guidelines. JAMA 2023;330:1892-902.

  5. 5

    Farkas J. The Internet Book of Critical Care (IBCC). EMCrit Project; continuously updated.

  6. 6

    Holst LB, Haase N, Wetterslev J, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock (TRISS). N Engl J Med 2014;371:1381-91.

  7. 7

    Carson JL, Brooks MM, Hebert PC, et al. Restrictive or liberal transfusion strategy in myocardial infarction and anemia (MINT). N Engl J Med 2023;389:2446-56.

  8. 8

    Kaufman RM, Djulbegovic B, Gernsheimer T, et al. Platelet transfusion: a clinical practice guideline from the AABB. Ann Intern Med 2015;162:205-13.

  9. 9

    Tomaselli GF, Mahaffey KW, Cuker A, et al. 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants. J Am Coll Cardiol 2020;76:594-622.

  10. 10

    Baharoglu MI, Cordonnier C, Al-Shahi Salman R, et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH). Lancet 2016;387:2605-13.

  11. 11

    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;86:1327-30.

  12. 12

    Wada H, Thachil J, Di Nisio M, et al. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost 2013;11:761-7.

  13. 13

    Iba T, Nisio MD, Levy JH, Kitamura N, Thachil J. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open 2017;7:e017046.

  14. 14

    Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv 2018;2:3360-92.

  15. 15

    Lo GK, Juhl D, Warkentin TE, et al. Evaluation of pretest clinical score (4 T's) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 2006;4:759-65.

  16. 16

    Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost 2020;18:2496-502.

  17. 17

    Bendapudi PK, Hurwitz S, Fry A, et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies. Lancet Haematol 2017;4:e157-64.

  18. 18

    Scully M, Cataland SR, Peyvandi F, et al. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura (HERCULES). N Engl J Med 2019;380:335-46.

  19. 19

    Kietaibl S, Ahmed A, Afshari A, et al. Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care: second update 2022. Eur J Anaesthesiol 2023;40:226-304.