haem emergencies nadim j lalani md july 24. 2008
TRANSCRIPT
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
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)
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
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?
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.
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
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)