DIC & Coagulation Disorders

Sarah McPherson & Mark Scott

January 17, 2008

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?

Hemostasis 101•Primary hemostasis - PLT mediated•Secondary hemostasis - fibrin mediated

Primary Hemostasisplatelet aggregation

Primary Hemostasisplatelet plug

Secondary Hemostasis Coagulation Cascade - Fibrin crosslinkage

PeT PiTT bull

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: ?

PLTs vs Factors

PLT Disorders

DestructionDecreased Production

Sequestration

Immune Non-immune

ITP TTPDICHUSHELLPSepsis

splenomegaly

Marrow failure

Quantitative Qualitative

ASA, plavixrenal and hepatic disease,vWD

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

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

Drugs that cause Thrombocytopenia

Most Common:• Heparin**• Gold salts**• Sulpha• Quinine• Ethanol (chronic)**• ASA• Indomethacin• Valproate

Rarely:• Heroin• Furosemide• Procainamide• Digoxin• Ranitidine• clopidogrel

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

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

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

DIC labsINR, D-dimerPLTSFibrinogen • Schistocytes, fragmented RBCs• Renal failure• Hepatic failure

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

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

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/severe based on percent of factor

activity– >5%, 1-5%, <1% respectively

• Most commonly hemarthrosis and SC bleeding

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

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)

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

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: ?

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

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

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)

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

Clinically Significant Bleeding may occur if

• INR >1.5• PTT >55• Fibrinogen <100mg/dL• PLTs <50

Hemostasis Achieved if

• Clotting factors approx >20-30%• Fibrinogen >100mg/dL• PLTs >50

1 Unit of Blood = 500cc

• 225cc pRBCs• 225cc FFP• 50cc PLTs• 25cc cryoprecipitate

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

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

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

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

Massive Transfusion

• 1:1:1 ratio Malone 2006

– Start PLTs and FFP after 4u of pRBCs

Massive TransfusionComplications

• Dilutional coagulopathy consider if replacing > 100% blood volume Hiipala et Al. Test PT/PTT if replaceing 50% BV

• Consumptive coagulopathy consider in Trauma and Obs due to release of TF into bloodstream

• Hypothermia if blood products <370

• Citrate Intoxication (Hypocalcemia)

• Metabolic Acidosis• HyperKalemia• Volume Overload

Trauma in the coagulopathic patient

• Recognize stage of hemorrhagic shock– 0-15,,15-30, 30-40, >40 (like tennis)

• Early administration of antidotes and factor– Hemophilia - 50u/kg rVIII– Add rVIIa as indicated

The Bleeding Kid• High index of suspicion and broader Ddx• Error on the side of over-investigation

– In history include FMHx– PE: include mouth, skin, abdo, joints– If concerned - consult

• rVIII dose as per adult• 1:1:1 rule for transfusion• ITP will be the most common bleeding dso

Bleeding in Pregnancy• TTP vs HELLP

– HELLP complications• Spontneous hepatic/splenic hem, placental abruption, ICH• Tx as per PIH and emergent delivery.

• Neither UFH or LMWH crosses placenta• Post-partum hemorrhage

– T uterine atony oxytocin– T retained tissue removal vs. D&C– T trauma (iatrogenic) surgical repair/hyst– T thrombophilias urgent correction

• Remember you have 2 pts – Fetal heart rate monitoring +/- U/S

What’s new

• Recombinant factor VIIa• Anti-Thrombin III• Protein C

Recombinant VIIa• Developed for Hemophilia pt with VIII & IX inhibitors. Promotes

hemostasis through extrinsic pathway.• Safe in high doses Hedner 2007

– Only works on bleeding areas– Review showed VTE in 1.5% (165 of 11,000 pts)

• Known benefits in chronic Hemophilia • Shown to prevent bleeding in radical prostatectomy, attenuate

ICH, and ?trauma• Trend towards decr Bleeding and Incr Mortality• Still under investigation in CHR but may be used as part of

study in conjunction with Trauma team.• Contra-indicated in DIC and high risk VTE

Acknowledgments• Sarah McPherson • Rob Hall & Shawn Dowling

www.remergs.com• Adam Oster• EM Rap

References1. Stanworth SJ, Birchall J, Doree CJ, Hyde C. Recombinant factor VIIa for the prevention and treatment

of bleeding in patients without hemophilia. Cochrane Database of Systematic Reviews 2007, Issue 22. Tintinelli pp 1319-633. Hedner U. Recombinant factor VIIa; its background development and clinical use. Curr Opin Hematol

2007,14:225-9.4. Drumond et Al. The massively bleeding patient. Anesthesia Clin North Am. 2001, 19(4)5. EM Rap. Sanja Aroarha. Hematologic Emergencies. October 2005 CD 2. 6. Malone DL et Al. Massive transfusion practices around the globe and a suggestion for a common

massive transfusion protocol. The Journal of Trauma Injury, Infection and Critical Care. 2006, 60(6);S91-6.