Transcript Disorders of Hemostasis Sultana Qureshi, PGY-2 Resident Rounds

Disorders of
Hemostasis
Sultana Qureshi, PGY-2
Resident Rounds
March 1, 2007
Thanks to Adam Oster for some slides!
Goals
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Approach and when to be suspicious
Pattern of presentation
ED Management – when to use blood products
Hemostasis
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Endothelial cells
Platelets
Blood flow & vasoconstrictors
Clotting cascade
Fibrinolysis
Approach to Bleeding Disorders
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Primary Hemostasis
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Exposed endothelial cells
cause platelets to
aggregate and form plug
Platelet Disorders
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ITP
TTP
Also partially in liver
disease, vWD
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Secondary Hemostasis
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Tissue factor iniates
coagulation cascade
eventually leading to
fibrinogen forming fibrin
cross links
Extrinsic starts pathway,
intrinsic sustains
Coagulation Disorders
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vWD
Hemophilia A & B
Other – consumptive
(DIC)
When to be suspicious
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Petechiae, Purpura, Ecchymosis
Nature of bleeding/sites
Significant or multiple episodes
Signs of previous bleeding
Medications (anti-coagulants)
Associated disease: liver disease, sepsis
Massive transfusion
FHx
Other important historical/physical info to
know???
Approach to Bleeding Disorders
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Platelet Disorder
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Immediate onset
Superficial bleeding
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Petechiae/Ecchymoses
(mucocutaneous)
GI/GU bleeding
Menorrhagia, epistaxis,
melena
Plt or Bleeding Time abn
PT/PTT N
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Coagulation Factor Disorder
Delayed onset (hours/days)
Deep bleeding
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Intramuscular
Intraarticular
Retroperitoneal
Hematuria
Hemarthrosis/hematomas
Less common to have
menorrhagia, epistaxis, etc
Plt and BT N
PT/PTT abn
Labs
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CBC, plts
PTT (intrinsic) – I, II, V, VII, IX, X, XI, XII
INR (extrinsic)– I , II, V, VII, X
Peripheral smear
Fibrinogen
D-dimer
FDP
Factor levels
Thrombin time
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What and how do you measure bleeding time?
When is it useful?
Blood Products
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Platelets – 1 unit raise value by 5-10
Cryoprecipitate – FVIII, vWF, fibrinogen,
fibronectin
FFP – contains all coagulation factors (about 7%
of a 70kg person)
Case
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25F – 32 wks GA presents with decr. LOC
Husband states had intermittent abdo pain X 2
days, suddenly got worse today
Vitals: 120, 90/50, 18, 99% 2L NP, 36.5
Doppler – fetal bradycardia
Uterus is tender and tense
DIC - Causes
• Sepsis/severe infection (any
microorganism)
• Vascular abnormalities
–Kasabach-Merritt Syndrome
–large vascular aneurysms
• Trauma (eg, polytrauma, neurotrauma,
fat embolism)
• Severe hepatic failure
• Organ destruction (eg,severe
pancreatitis)
• Malignancy
–solid tumors
–myeloproliferative/
lymphoproliferative
• Severe toxic or immunologic
reactions
–snake bites
–recreational drugs
–transfusion reactions
–transplant rejection
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• Obstetrical calamities
–amniotic fluid embolism
–abruptio placentae
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Hypothermia
Acidosis
Pathophysiology
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Unifying cause relates to widespread endothelial damage with
extensive cytokine release
DIC is a spectrum, may have thrombosis or bleeding or both
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Activation of procoagulant pathway
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Endothelial damage
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Liver disease, splenectomy
Vascular stasis
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Sepsis, vasculitis, aneurysm, hemangioma
Reticuloendothelial injury
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Hemolysis, tissue injury, malignancy, fat embolism, heat stroke
Hypotension, hypovolemia, PE
Other
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Acute hypoxia/acidosis
Clinical Features
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Signs of Microvascular
Thrombosis (10-40%)
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Neuro
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Skin
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ARDS
GI
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Oliguria, azotemia, cortical
necrosis
Pulmonary
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Focal ischemia, superficial
gangrene
Renal
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Multifocal, delirium, coma,
seizures
Acute ulceration
RBC
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Microangiopathic hemolysis
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Signs of hemorrhagic
diasthesis (more common)
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Neuro
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Skin
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Petechiae, echymosis, oozing
Renal
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IC bleed
hematuria
Mucosal
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Gingival oozing, epistaxis,
massive bleed
Labs
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Consumptive Coagulopathy
↓Plts
 ↑PT, ↑PTT
 ↓Fibrinogen (careful in sepsis)
 +D-dimer (DIC)
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DIC Scoring System
Bakhtiari K et al. Critical Care Med. 2004;32:2416-2421.
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Step 1. Risk assessment: does the patient have an underlying disorder known to be
associated with overt DIC? If yes, proceed. If no, do not use this algorithm.
Step 2. Order global coagulation tests: platelet count, prothrombin time (PT),
fibrinogen, soluble fibrin monomers, or fibrin degradation products.
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Step 3. Score global coagulation test results:
• platelet count (> 100 = 0, < 100 = 1, < 50 = 2)
• elevated fibrin-related marker (eg, soluble fibrin monomers/fibrin degradation
products) no increase: 0; moderate increase: 2; strong increase: 3*
• prolonged prothrombin time (< 3 sec. = 0, > 3 but < 6 sec = 1, > 6 sec = 2)
• fibrinogen level (> 1.0 g/L = 0, < 1.0 g/L = 1)
Step 4. Calculate score.
Step 5. If ≥5: compatible with overt DIC; repeat scoring daily. If <5: suggestive (not
affirmative) for non-overt DIC; repeat next 1–2 days.
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* In the prospective validation studies, D-dimer assays were used and a value above the
upper limit of normal was considered moderately elevated; whereas, a value above five
times the upper limit of normal was considered a strong increase.
DIC Scoring System
Bakhtiari K et al. Critical Care Med. 2004;32:2416-2421.
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Sens 93%
Spec 96%
Management
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TREAT UNDERLYING CAUSE!!!
Blood Products
Only if active bleeding or high risk of bleeding (ie. early
post op or pre-invasive procedure)
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Platelets
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Bleeding – tranfuse if count <50
No bleeding – transfuse if <10-20
FFP
Cryoprecipitate
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If fibrinogen <2
1-4U/10 kg
Novel treatments
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APC – up to Phase III trials show benefit in
septic DIC
TFPI – promising
ATIII- RCT promising
Heparin
Only case series. Controversial
 Therapeutically if overt venous TE or purpura
fulminans
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Case
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22M presents with seizures, decr. LOC, jaundice and
fever
Purpuric rash over body
V: 60, 110/70, 16, 96% RA, T=38.3
Hb 90, WBC 8.0, plt 20
PT/PTT N
Cr 130, small hematuria
T.bili 60 other LFTs N, LDH 500
Ddx?
D-dimer/fibrinogen?
TTP
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Main ED mgmt point:
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NO platelet transfusion unless life threatening
hemorrhage
Liver Disease
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What mechanisms of coagulopathy?
What blood products to use?
Liver Disease
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Why they bleed?
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Thrombocytopenia from hypersplenism (portal HTN)
Platelet dysfunction
Reduction in absorption of Vit K dependant factors (2, 7, 9,
10)
Reduction in synthesis of most factors
Dysfibrinogenemia (abn fibrinogen synthesis)
Enhanced fibrinolysis (decr. Plasmin inhibitor)
In bleeding ER – may require transfusion of many different
products (RBC, plts, FFP, cryo)
Vs. DIC???
Case
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6F with epistaxis (has had multiple mild episodes in
past 2d)
Also history of spitting up blood in morning
Examine mouth and see blood oozing from gums when
scraped with tongue depressor
Otherwise well other than flu 3 weeks ago
Notice petechiae around sock elastic
Dx?
Lab results?
Acute ITP
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Usually children 2-6
M=F
Usually have had recent infection
Abrupt onset of bleeding (vs insidious)
Platelets <20
Usually lasts week
80% spontaneous remission
Management: IVIG if bleeding significant of plts <10
-splenectomy in very severe cases
Chronic ITP
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MCC of isolated thrombocytopenia
Adults (20-40 yo), F>M (3:1)
No precipitating infection
Insidious bleeding (heavy periods, easy bruising)
Plt 30-80
May last months to years, and uncommon spont.
Remission
Mgmt: steroids, IVIG, splenectomy
Need w/u for other causes of thrombocytopenia! Esp
if older (ie malignancy)- Smear
Major concern is cerebral hemorrhage is plt<5
Platelet Disorders
Quantitative
Destruction
Immune
Decreased
Production
Qualitative
Sequestration
Non-immune
splenomegaly
ITP
TTP
DIC
HELLP
Sepsis
Marrow failure
ASA, plavix
rena and
hepatic
disease,
vWD
Case
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12F hx of VWD
Presents with heavy menarche (ongoing
bleeding for >7 days)
Pale, asymptomatic
Hb = 60
Mgmt?
Erik Adolf von Willebrand
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1870-1949
Finnish Pediatrician
“known for integrity and
modesty”
Hjordis – 5 yo girl with
FHx of bleeding
disorders
Von Willebrand’s Disease
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AD
Qualitative vs. quantitative abn
Different sized multimers
vWF has 2 jobs
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Platelet adhesion, carrier for Factor VIII
New Classification
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Type 1: mild quantitative defect (75%)
Type 2: qualitative defect (impaired fxn)20%
Type 3: severe total quantitative defect (rare)
Management
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Type 1
Usually mild symptoms (mucocutaneous bleeding
sources)
 Mgmt: DDAVP 0.2 mcg/kg IV/IM/IN
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Type 2 or 3
More likely to have mod-severe symptoms incl. soft
tissue hematomas, GI bleeds, hemarthroses
 Mgmt: Cryoprecipitate +/- DDAVP +/- Humate P
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Case
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50M slipped on ice and twisted R knee
On exam: large hemarthrosis
What is most likely hemostatic disorder?
Management?
Hemophilia
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A – FVIII deficiency
B – FIX deficiency
X-linked recessive
Mild/mod/severe is based on factor activity
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5-30%, 1-5%, <1%
PTT prolonged (if factor activity <30%) PT N
However, if mild hemophilia, PTT may be N
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Bleeding first noticed usually in early years
5 Hs:
Hemarthroses
 Hematomas
 Hematochezia
 Hematuria
 Head hemmorhage
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Recurrent hemarthroses lead to joint damage
IC bleed is major cause of death
Also, tend to bleed LATE – days after minor injury
Therefore treat aggressively
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Goal to achieve 30-100% factor activity
Options: Specific factor replacement, cryo, FFP
Consider: Severity of bleeding, disease severity and
availability of products
Always consider factor activity is zero in ED!!!
Factor Replacement
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Is ideal if available in ED, otherwise cryo
1U/kg will increase factor by 2%
May develop alloantibodies and need 3-4X
predicted dose
Goals:
Mild: 5-10% activity desired -initial dose 12.5U/kg
 Mod
20-30% - 25U/kg
 Severe >50% - 50U/kg
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Cryoprecipitate
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Contains 80- 100U FVIII (als contains vWF, fibrinogen,
FXIII and fibronectin)
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Considered a second line agent for Hem A
Dose = 2bags/10kg to raise FVIII to hemostatic
levels
T ½ = 8hrs
FFP
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Fluid portion of blood separated at 18C then
frozen
Contains all coagulation factors
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Approx 7% of of all coag factor activity of a 70kg
person
Not routinely used as factor replacement in
Hem A
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Could consider if nothing else available
Case
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25M hemophiliac
Tripped on stairs and fell from 1ft height
Hit head on floor. No LOC, NV. Feels fine
Management?
Mgmt
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All hemophiliacs with any trauma need
admission for observation
Minor head trauma can be life threatening
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Give Factor VIII to 50% activity BEFORE CT
Take Home Points
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Approach to bleeding disorders
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High index of suspicion
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Difference in presentation of platelet
dysfunction vs. coagulation factor d/o
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When to give blood products?
Take Home Points
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DIC – treat underlying cause
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vWF – important to know type
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Hemophilia – aggressive therapy with factors
Quiz
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Which of the following is least likely due to a
platelet disorder?
A) Epistaxis
 B) Retroperitoneal Bleeding
 C) Ecchymoses
 D) Petechiae
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Quiz
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Which is least likely associated with coagulation
factor deficiency?
A) Intra-articular bleeding
 B) Delayed bleeding
 C) Retroperitoneal Bleeding
 D) Petechiae
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Quiz
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Which clinical finding is MOST COMMONLY
associated with the onset of ITP?
A) Ecchymoses
 B) Purpura
 C) Petechiae
 D) Gingival bleeding
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Quiz
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Which of the following are true of chronic ITP?
A) More likely in female children
 B) Spontaneous remission typical
 C) Underlying disorder is autoimmune
 D) Platelet transfusion is initial, definitive therapy
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Quiz
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Which lab finding is more indicative of liver
disease vs DIC?
A) Thrombocytopenia with bleeding
 B) Prolonged PT
 C) Decreased fibrinogen
 D) Normal or min. elevated D-dimer
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Quiz
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50M cirrhotic with ascites presents with SBP.
HD stable and no active bleeding
Prolonged PTT, INR
Low platelets and fibrinogen
What to give prior to paracentesis?
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A) Cryo
B)FFP
C)Platelets
D)DDAVP
Quiz
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Most commonly observed lab abnormality in
DIC?
A) Long PTT
 B) Thrombocytopenia
 C) Low fibrinogen
 D) elevated D-dimer
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Quiz
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What is the most appropriate analgesic for a
patient with Type 1 vWD?
1) ASA 80
 2) ASA 325
 3) Ibuprofen
 4) Acetaminophen
 5) Naprosyn
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Quiz
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9M with Type 1 vWD presents with mild
gingival bleeding after flossing.
Stable, however slow bleeding has continued for
hours despite local pressure
Most appropriate treatment?
Quiz
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19M restrained back seat passenger, rear ended
at 35 kph. Hit head on front seatback. No LOC.
No neck pain. Ambulatory on scene.
Exam normal except small contusion to
forehead.
History of Hemophilia B
Mgmt?
Quiz
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7M presents with LLQ pain after being “knee’ed” by a
bully at school 2 hours ago
History of Hemophilia A “severe”
VSS, contusion in L inguinal area, mildly tender
Pain with extension of lower extremity, and walks
flexed at the torso with a limp
Next step?
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A) Give Factor VIII and CT Abdo
B) Give Factor IX and CT Abdo
C) Give DDAVP and CT
D) Give FFP and US Abdo