DIC & Coagulation Disorders

1. DIC & Coagulation Disorders Sarah McPherson & Mark Scott January 17, 2008

2. Objectives: • Physiology of coagulation • Comparison of PLT vs. factor disorders • Congenital Coagulopathies • Basics of blood products and how much to give • Trauma in the coagulopathic patient. • Guidelines & Complications of Massive Transfusion • Indications for factor VIIa • Management of Iatrogenic coagulopathy • warfarin, heparin & thrombolytics • Special populations • Pediatrics • Pregnancy • What’s new?

3. Hemostasis 101 Primary hemostasis - PLT mediated Secondary hemostasis - fibrin mediated

4. Primary Hemostasisplatelet aggregation

5. Primary Hemostasisplatelet plug

7. Secondary Hemostasis Coagulation Cascade - Fibrin crosslinkage PeTPiTT bull

10. Case 1 • 26 F G1P0 20 weeks gestation fever and skin rash • PE: T 385, purpura chest and legs, Fluctuating LOC and L hemiparesis. • Labs: Hg 100, PLTs 5, INR 1.0, PTT 31, schistocytes • Dx: TTP • Rx: ?

11. PLTs vs Factors

12. PLT Disorders Quantitative Qualitative Decreased Production Sequestration ASA, plavix renal and hepatic disease, vWD Destruction Immune Non-immune splenomegaly TTP DIC HUS HELLP Sepsis ITP Marrow failure

14. ITP • Immune Thrombocytopenia purpura = acquired hemorrhagic dso with immune destruction of PLTs • Peaks in children 2-6 • Note: differing presentation in Adults vs. Children • Usually post viral IgG attack on PLTs Ag • PLT but functional • Sudden onset lasting a few weeks (rarely chronic) • Diagnosis of exclusion (usually no splenomegaly) • Suportive care for mild (PLT>50,000) • Tx for bleeding or PLT<20,000) • Steriods x 4 weeks +/- IVIG for mod/severe

16. TTP • Thrombotic Thrombocytopenia Purpura = PLT deposition and aggr in capillaries • Presents with Thrombocytopenia, MAHA, (most common) Fever, purpura, neuro symptoms • Pregnancy (2nd Trim) is more common precipatant. Also sepsis, Malig, vasculitis, SLE, drugs • Labs show PLTs, schistocytes, HA, haptoglobin • Tx: Supportive + Plasmapheresis +/- steroids +/- splenectomy • 80-90% mortality if not treated

18. Most Common: Heparin** Gold salts** Sulpha Quinine Ethanol (chronic)** ASA Indomethacin Valproate Rarely: Heroin Furosemide Procainamide Digoxin Ranitidine clopidogrel Drugs that cause Thrombocytopenia

20. HUS • Hemolytic Uremic Syndrome = usually toxin mediated damage to renal tubules and glomerulus resulting in MAHA and PLT thrombi • Usually during or following diarrheal illness (EC 0157:H7) • Mortality 5-15%, worse in kids • Most common cause of renal failure in kids • Supportive Therapy +/- steriods

22. DIC • Disseminated intravascular coagulation = sick pts. active TF causing massive microvascular deposition of fibrin accel thrombolysis and coagulation at same time • Results in consumption of PLTs, factors, fibrinogen, HA, production of FDPs • Clinical presention: • Multi-organ dysfunction form bleeding/coagulation • Renal failure, ACS, neuro abn, ARDS, ischemic colitis, etc • Extensive skin, incision and MM bleeding

23. Etiology of DIC • Most common: sepsis (esp gm neg) • Cancer (remember Trousseau syndrome), adeno, Lymphoma. Leukemia • Trauma, post-op • Liver ds • Vascualr disease • Pregnancy • ARDS • Transfusion rxns • Toxins: snake bites, drugs, stimulants

24. DIC labs • INR, D-dimer • PLTS • Fibrinogen • Schistocytes, fragmented RBCs • Renal failure • Hepatic failure

25. DIC Treatment • Supportive and management of underlying Dso • Definitive TX depends on presentation • If Bleeding • Fibrinogen (~10u cryoprecipitate) • Factors (~4u FFP • PLTs if less than 50,000 (6u) • If Thrombosis (or purpura fulminans) • Heparin or LMWH • Protein C and AT III - under investigation

27. Case 2 • 8 yo M present to PLC with painful swollen R knee 2 days after fight with his brother • Delayed bleeding from lacs • PE: R knee is swollen, erythematous, cool, remaining exam N. • Hg 140, PLTS 350, PTT = 90, INR 1.0 • Dx: Hemophilia • Tx: recombinant VIII

28. Hemophilia • A  Deficiency of factor VIII (1 in 10,000 M) • B  Deficiency of factor IX (1 in 30,000 M) • Life-expectancy now 60yrs • X-linked recessive • Mild/moderate/severebased on percent of factor activity • >5%, 1-5%, <1% respectively • Most commonly hemarthrosis and SC bleeding

29. Treatment for Hemophilia • Recombinant factor VIII • Dependent on severity • Mild 12.5u/kg • Moderate 25u/kg • Severe or signif bleeding 50u/kg • Go slow 3cc/min IV to avoid anaphylatoid rxn • Also consider: • FFP (200u per unit) • Cryoprecipitate (80u per unit) • 15% will develop alloantibodies (IgG) against FVIII which neutralize exogenous administration. Pts will require 3-4X the dose of replacement. • Give recombinant factor VIIa

31. Von Willebrand Disease • Large multimeric glycoprotein involved in PLT aggregation and VIII • 1% of population • Type 1 - decr vWF (80%) • Type 2 - abn vWF • Type 3 - none (rare) • Usually asymptomatic unless challanged (surgery or trauma)

32. Treatment for vWD • ddAVP • Induces release of vWF from endothelium • ? Secondary effect promoting hemostasis • 0.3ug/kg SC inj, max of 20ug every 12 hrs prn • Children - nasal spray • Cryoprecipitate second line or type 2 & 3 • Female pts can take OCP

33. Case 3 • 79 M acute CVA presented 2hrs post onset • Nurse calls you to bedside re: Decr LOC • N CT head, stroke team involved • TPA was given 30mins prior • Tx: ?

35. Management of Iatrogenic Coagulopathies • Warfarin (guilelines from “Chest” 2004) • INR 2-5 hold or reduce • INR 5-9 Vit K 1mg po • INR 9-20 Vit K 5mg po/IV • INR >20, or signif bleed FFP and Vit K 10mg po/IV • **be careful in High risk pts (Afib w/ VD, mech V) • Heparin & LWMH* • Thrombolytics

36. Management of Iatrogenic Coagulopathies • Warfarin • Heparin • Protamine 1mg/100mg Hep in last 4 hrs • FFP • RBCs and PLTs if indicated • LMWH • Less bleeding complications • Protamine 1mg/1mg Enoxaparin • Thrombolytics

37. Management of Iatrogenic Coagulopathies • Warfarin • Heparin & LWMH* • Thrombolytics - Converts Plasminogen to Plasmin • Stop TPA, stat CT head • Cryo +/- FFP +/- RBCs • +/- Transexamic acid 5g IV over 60mins, or • e-aminocaproic acid 10mg/kg q6H • Clopidogrel/ASA • Give PLTS (goal >50,000)

39. Approach to Massively Bleeding Patient • ATLS • Target correction of CVP, MAP, Hg as in sepsis. • Mortiality benefit shown for correction of serum Lactate and pH Drummond et Al , 2001

40. Clinically Significant Bleeding may occur if • INR >1.5 • PTT >55 • Fibrinogen <100mg/dL • PLTs <50

41. Hemostasis Achieved if • Clotting factors approx >20-30% • Fibrinogen >100mg/dL • PLTs >50

43. 1 Unit of Blood = 500cc • 225cc pRBCs • 225cc FFP • 50cc PLTs • 25cc cryoprecipitate

44. Packed RBCs • 225cc concentrate RBCs, hct ~80-90% • 1 unit raises Hg by ~10mg/L • Oneg available immediately, typed blood 15mins, type and cross match 1 hr • Tranfuse if: • <70 & stable • <80 & bleeding • <100 & acute coronary syndrome

46. FFP • Fluid portion of blood separated at 180C then frozen (~225cc) • Contains all Coag factors and some fibrinogen • 1 unit replaces approx 5-10% of factors • Should be ABO compatible • Give 4 u at a time

48. Platelets • PLTs isolated from plasma (50cc) • Replace according to ABO compatibility • 1 unit will incr PLTs by approx 10 (variable) • Give 6u at a time

50. Cryoprepitate • plasma fraction that contains factor VIII, vWF, fibrinogen (~50cc) • obtained by harvesting the precipitate that forms when frozen plasma is warmed to 4°C. • 1 bag contains approx 100U of vWF and FVIII • Used for bleeding if Fibrinogen <100, or VWD not responding to ddAVP • Give 10u at at time