haem emergencies nadim j lalani md july 24. 2008

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Haem Emergencies Nadim J Lalani MD July 24. 2008

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Haem Emergencies

Nadim J Lalani MDJuly 24. 2008

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David Dwight “Ike” Eisenhower: 1890-1969

Former general 34th US Pres (1953–1961). Served 2 terms

Avid golfer Hcap of 18. Broke 80 3 times. Had 1 hole in one.

Played 800+ rounds in 8 years as President.

Was one of the 1st people on Coumadin

Parents were JW’s

Ike Continued Member at Augusta Hated the Loblolly

pine off the tee on the 17th

Petitioned to have it cut down.

Now named after him.

Objectives Review hemostasis Work through cases. By the end, you should know how to

manage: DIC ITP Hemophilia and V W dis Coumadin and Heparin overanticoagulation Complications of thrombolytic

Hemostasis: Steps 1 and 2 Vessel constriction Primary Hemostasis:

exposed collagen VWf attaches gathers plts and fibrinogen = platelet plug

Mucocutaneous bleed

Clotting: Step 3 Secondary Hemostasis:

Clotting Factors Factor VII = extrinsic [gets used up

quick] Intrinsic = PTT, Extrinsic = PT Prothrombin thrombin

fibrinogen fibrin

Clotting Cascade

Step 4: Breakdown Plasminogen

Plasmin

Fibrin FDP’s

Case 1 4 yo F brought in

by parents for this “rash”. URTI 2 weeks ago

Case 1: petechiae(muco)Cutaneous Pinpoint dots of

blood. DON’T BlanchLarger flat areas =

purpura.Very large area =

ecchymosis.NB most common cause of petechiae in kids is prolonged/persistent valsalvas ie coughing ... See it in upper torso [SVC] distribution.

Platelet problems

DestructionDecreased Production

Sequestration

Immune Non-immune

ItP TTPDICHELLPSepsis

splenomegaly

Marrow failure

Too Few Don’t Work

ASA, plavixrena and hepatic disease,vWD

Dr. A. Oster

ITP What? Autoantibodies cause thrombocytopenia Who?Children 2-6, M=F Pathophys: IgG usually against membrane GP’s

(75% anti-Giib/iiia) spleen eats up plts Features: preceded by viral illness 3 weeks

before onset, 1% CNS bleed, 10% other signif bleed, almost no mortality

LAB:Plts usually <20 [can have anemia]

ITP: Treatment No consensus

Platelets > 30,000/mL No Tx. Outpatient f/u Platelets < 20,000/mL PO steroids [+/- IVIG]

+/- admit. Platelets < 10,000/mL or signif bleeding. IV

steroids/ IVIG [high dose better] admit

Idiopathic Thrombocytopenic Purpura: A Practice Guideline Developed by Explicit Methods for The American Society of Hematology

By James N. George, Steven H. Woolf, Gary E. Raskob, Jeffrey S. Wasser, Louis M. Aledort, Penny J. Ballem, et.al

Transfusions anyone? Only if severe bleeding

Adults: look for other causes [esp > 60 yo cancer/myelodysplasia]

ASH Guidelines for Adults : [confusing] Plts > 50,000 NO Rx [unless signif bleed or risk factors

[htn/pud] Plts > 30,000 and asympt NO IVIG Plts 20,000 and asymptomatic/mild purpura NO admit Plts 20,000 – 30,000 and bleeding Treat “steroids

appropriate” Plts ,20,000 treat and admit

Rhogam? Works if Rh + and is $1000 US cheaper than IVIG. [50mcg/kg] Increased Plt Count initially better IVIG vs Steroids/Anti D Some argument for no treatment Standard of care in N.Am / Calgary is IVIG/Steroids/admit

Case 2 33 yo G2P1 @ 22 wks GA Presents vomiting with abdominal pain and

malaise BP 150/90, 105, 20, sats 99% Jaundiced, tender RUQ Labs

Hb 90, PLT 80, inc ALT/AST/bili Coags normal Ddx?? http://www.aafp.org/afp/990901ap/829.html

Dr A Oster

Case 3 60M with ESRD

comes in septic with this During w/u note that

INR and PTT up What is going on? Futher w/u?

DIC complex systemic thrombohemorrhagic

disorder involving consumption of coag factors and platelets.

characterized by generalized bleeding ranges from petechiae exsanguinating

hemorrhage

Also get thrombosis. Seen in 30-50% septic pts & carries 20-50%

mortality

Table 1. Conditions underlying DIC syndrome

InfectionsAcute DIC: Bacteria and their toxins, fungi, viruses, rickettsiaeChronic DIC: Any chronic infection (eg, tuberculosis, abscesses, osteomyelitis)

Noninfectious inflammatory diseasesInflammatory bowel disease: Crohn's disease and similar disorders

Obstetrical complicationsAcute DIC: Abruptio placentae, abortions (especially therapeutic abortions), amniotic fluid embolism, hemorrhagic shockChronic DIC: Dead fetus syndrome

MalignancyAcute DIC: Acute promyelocytic leukemia, acute myelomonocytic or monocytic leukemia, disseminated prostatic carcinomaChronic DIC: Lung, breast, gastrointestinal malignancy

Vascular diseaseAcute DIC: Brain infarction or hemorrhageChronic DIC: Aortic aneurysm, giant hemangioma

VenomsAcute DIC: Snake, spider (rare)

TraumaAcute DIC: Massive tissue destruction, brain damage

OthersAcute DIC: Heparin-induced thrombocytopenia with thrombosis (HITT), purpura fulminans in newborns (homozygous protein C deficiency)

Lab: Plt low INR high PTT high FDP positive/high Fibrinogen low DIC D-Dimer positive

DIC Treatment ABC’s don’t forget Calcium [check ABG] Treat underlying cause RBC’s Plts

Maintain >30 or higher if OR planned 1U plts contained 5x109 plt expected to raise plasma by same

FFP If DIC assoc with increased INR and PTT

Cryo If fibrinogen <2 Give 1-4U/10kg

AT III:

DBRCT 2300 pts

ATiii [30,ooo IU over 4 days] vs Placebo

Outcomes: 10 28d mort; 20 ICU stay, 50d mort

No Difference , but “trend” in No-heparin sub group

Publication of a sub group analysisHigh-dose antithrombin III in the treatment of severe sepsis in patients with a

high risk of death: Efficacy and safety

Wiedermann,, et.al

Critcal Care Medicine Volume 34(2), February 2006, pp 285-292

1000ptsBetter 90d survival with AT iiiEven better with no heparin 10% better survivial

 

Treatment effects of high-dose antithrombin without oncomitant heparin in patients with severe sepsis with or without disseminated

intravascular coagulation.

Kienast J, Juers M, Wiedermann CJ, Hoffmann JN, Ostermann H, Strauss R, Keinecke HO, Warren BL, Opal SM;

J Thromb Haemost. 2006 Jan;4(1):90-7.

•Another analysis of the same “no heparin” subgroup•Treatment with ATiii ARR 14%

•Subgroup analyis of PROWESS study•APC vs Placebo in pts with DIC•NO benefit and increased bleed risk

• Heparin: benefit only in case reports NOT RCT’s

•Use if theombosis going on

•Future: Target TF pathway with TFPI / iFVIIa / rNAPc2 [phase ii trials]

Other:

Case 4 7 mo girl Vomiting/lethargic/febrile GM Sz in WR O/E:

Febrile/Tacchy w/ bulging fontanelle lethargic

MGMT? Ddx? LAB:

Hb 60, PTT 90 LP: + RBC’s and Xanthochromia

MGMT NOW Dr.?

Haemophilia : Two kinds:

88% Haemophilia A Factor VIII def Haemo B [aka Xmas] Factor IX def

Haem A: X-linked recessive 30% no family Hx [1/3 spontaneous

mutation] Increased aPTT unless F Viii > 30%

Haemophilia Classification: [based of percent factor

activity] Mild >5%, Moderate 1-5% Severe <1%

80-90% present as hemarthrosis to the ED [knee/ elbow] chronic haem = dibilatating

MC cause of death in haemophilia? ICH low threshold to scan head & treat prophylactically

Management Depends of severity of bleed:

Minor hemarthrosis/hematuria Moderate GI bleed/epistaxis/dental Severe CNS/airway/retroperitoneal

Haem A Haem B12.5 u/kg minor 25 u/kg25 u/kg moderate 25 u/kg50 u/kg severe 50 u/kg Above regimen should raise FVIII levels to

25%, 50% and 100%

Factor replacement Each u/kg of Factor VIII increases

factor levels by 2% Each u/kg of Factor IX increases factor

levels by 1%

Management Don’t forget other stuff:

Stitches/direct pressure/local epinephrine If you don’t know & signif bleed

assume factor activity is 0%

What if no Factor? Cryoprecipitate (2nd line):

Contains 100U FVIII (also contains vWF, fibrinogen, FXIII and fibronectin)

Dose = 2bags/10kg to raise FVIII to hemostatic levels T ½ = 8hrs

Can give FFP: Contains all coagulation factors Approx 7% of of all coag factor activity of a 70kg person

DDAVP: Increases VWf Good for mild cases

Case 5 38 y m just had tooth pulled. Bleeding

x6h Hx: easy bruising otherwise healthy Father doesn’t go to dentist for same

Ddx?

Von Willebrand’sDisease Most common inherited bleeding

dis [1% pop] AD [but can be AR] inheritance Affects mostly primary hemostasis

VWf big protein Binds platelets to collagen Carries Factor Viii in blood

Von Willebrand’s: Three types

Type I [70-80%]: Less VWf [therefore less F Viii]

Type II abc… [15-20%; AD/AR]: Non-functional VWf

Type III: absent VWf [ also affects F Viii]

Tend to present with mucocutaneous bleeding [except Type III]

LABS bleeding time? increased Platelets? N aPTT?/INR [increased PTT, N INR] factor VIII level? Low vWF antigen test

measures amount vWF Mild 20% to 40% Severe < 10%

Ristocetin test? abnormal How well the vWF is working

Treatment Options Want 40-50% VwF activity for minor bleed Want 80-100% for major bleeds [should then be

kept at >50% for a week after] DDAVP:

Increases vWf levels If Pt is a “responder” [NB! DDAVP Not enough

for major bleeding] Dose: IV 0.3 mcg/kg

IN [Stimate] 150 mcg [ 1 puff] if < 50kg

300 mcg > 50kg Don’t use the DDAVP reserved for DI [diluted]

Humate-P: Specific vWF and factor VIII replacement Each dose may vary in its vWf/FViii activity

Cryoprecipitate No longer indicated unless don’t have

Humate 1 bag contains approx 100U of vWF and FVIII

(approx 10x more than FFP) Non-R FViii?/FFP? Nope

Adjunct Drugs Tranexamic acid (Cyclokapron):

an antifibrinolytic agent [10x more potent than Amicar]

inhibits the activation of plasminogen plasmin. Dose: PO 25 mg/kg Q 6-8 [IV 10mg/kg Q6-12] Clot risk / Not available

Epsilon amino caproic acid (Amicar): Also Inhibits fibrinolysis Dose: 100 mg/kg/dose PO then 50mg/kg Q6

Topical thrombin and Fibrinogen Estrogen?

Case 6 60 yo with ACS

Got ASA, Heparin, bblocker Waiting for CCU Nurse asks you to see the pt’s rectal bleed Mechanism of heparin How do you reverse heparin?

Heparin Unfractionated heparin

Major sites of activity ATIII, Xa Other sites IIa, IXa, XIa

Anticoagulant effect largely through ATIII.

Produces a conformational change which accelerates the ability of ATIII to inactivate thrombin

How to reverse it? Protamine

T ½ = 60mins 1mg protamine neutralizes 100 circulating

units of UFH given in last 4h Max 50 mg Give slowly anaphylactiod rxn NB! Include bolus

What about LMWH? Inhibitor of Xa [some ATIII action] Activity 14-16hrs, T ½ is 4hrs Protamine can help but reversal is more

difficult < 8h post-dose:

Dose: 1mg protamine : 1mg Enoxaparin > 8h < 12h:

0.5mg [half dose] : 1mg >12h:

Nothing

Case 7: 90 y F on warfarin sent in from LAB

with INR of 10 What do you do?

Coumadin Vit K dependent coag factors:

II, VII, IX, X Cofactor in carboxylation of enzymes which

activate factor

Ptn C and S Measure INR T ½ = 2.5d

Who to reverse? Life threatening Have to ask why on warfarin:

High risk [15%/year stroke]: Mechanical MV AF with Valve dis

Low risk [1/1000 stroke]: DVT AF

EMrap treatment protocol: INR

<5.0 & no bleed skip dose5.0 – 9.0 & no/minor bld hold & 1mg VitK9 – 20 hold & 3mg VitK>20 10mg VitK & FFP

Case 8: 82 y M. On coumadin for Mechanical AV Falling to the Right. INR 4.4 Doctor? Told to hold dose. Went home took nap.

Awoke confused later in the Afternoon. O/e: GCs 14. Left weak. Left drift. Inc

DTR’s. Agnosia. Doctor?

Doctor?

Prothrobin Complex Octaplex® = 20ml vial of:

Factors II, VII, IX & X + Proteins C and S

Octaplex: Indicated:

Rapid Correction of VitK antagonists in the setting of:

Major bleeding Surgery imminent

Dose: no more than 120ml

Well studied Reversal in 15 min Lasts 6 h May cause

thrombosis/allergy Not tested in pregnant Costs $500/vial. $2500 for

max dose.

Case 9: 16 yo depressed swallowed a bunch of this Doctor?

Brodifacoum Poisoning Aka “super coumadins” Half life? 24-100 days Treat as with Warfarin OAC FFP’s [15ml/kg in Peads] Requires 50-800mg/day of Vitamin K Expect to treat for weeks/months

Vitamin K Activated VitK hq Catalyses

carboxylation of II,VII,IX,X, C, S

Oral takes 6h IV takes 1h

Case 60 with STEMI that you’ve thrombolyzed, now

ALOc and you scan him

TPA Converts plasminogen plasmin

Fibrin FDP’s

Reversing lytics Reversal

Stop lytic Replenish fibrinogen

Cryo FFP to correct prolonged bleeding

time PRBC’s Platelets Reverse heparin

Absolute lytic contraindications Hemorrhagic cerebrovascular accident intracranial neoplasm recent cranial surgery or trauma (10 days) uncontrolled severe hypertension Major surgery of thorax or abdomen (10 days) prolonged cardiopulmonary resuscitation current severe bleeding (e.g., gastrointestinal)