DIC/anticoagulation reversal

Question 1

What is the Pathophysiology of HIT?

Answer 1

HIT - thrombocytopenia but causes thrombotic problems, occurs w LMWH too; usually in 1st week

Question 2

What are the findings in HIT?

Answer 2

Thrombocytopenia: < 150, 50% decrease from baseline
Thrombosis: arterial or venous
Timing: generally 5-10 days after starting heparin
No other explanation
Necrotic skin lesions, skin necrosis

Question 3

What is the treatment for HIT?

Answer 3

Tx : stop heparin/LMWH; start alternative anticoagulant ( lepirudin, bivalirudin or argatroban), reverse warfarin. Avoid warfarin and avoid platelet transfusions

Question 4

Presentation of TTP-

Answer 4

10-40 yo female, thrombocytopenia, microangiopathic hemolytic anemia (schistocytes, frag RBC’s), fluctuating neuro sx, renal dz, fever.

Question 5

Findings in TTP-

Answer 5

Fever, anemia (microangiopathic hemolytic- Increased unconjugated bili, LDH, decreased haptoglobin), thrombocytopenia, renal abnormalities, neurologic
(thrombosis)
Low platelets, normal coagulation factors, normal fibrinogen, MAHA, platelet plugs

Question 6

Treatment of TTP-

Answer 6

Tx: Steroids, dialysis if renal failure, Plasma exchange dramatically ↓ mortality, FFP (gives back ADAMTS13)
-avoid plts

Question 7

Presentation of ITP?

Answer 7

ITP
Acute: 2-6 yo, prior viral prodrome, self-limited with in few weeks to months
Adults if have, usually present with platelets < 10,000

Question 8

Treatment of Acute ITP?

Answer 8

Tx : supportive care; if severe bleeding (platelets < 50,000) or platelet < 20,000
RBCs for resuscitation and anemia
Steroids: impaired clearance of Ab coated platelets
IVIG (1 gm/kg): <5,000 platelets and completed steroid course

Question 9

Treatment of Acute Pediatric ITP?

Answer 9

Pediatrics: controversial, usually self resolves, consider if concern for ICH- need to discuss with hematologist

Question 10

Treatment of Chronic ITP?

Answer 10

Chronic: mostly adult female, insidious onset, r/o other dz (SLE, lymphoma, etc)
Tx: consider steroids and splenectomy; life threatening bleed IV IgG and plt transfusion, immunosuppression, rituximab, thrombopoietin agonist
<50,000 and asymptomatic- no treatment
<50,000 and symptomatic- steroids
<20,000- IV methylpred
<20-30,000 with active bleeding- IVIG

Question 11

Treatment of ITP in pregnancy?

Answer 11

Pregnancy: count should be maintained > 30,000 and 50,000 near term

Question 12

Presentation of Hemolytic Uremic Syndrome

Answer 12

HUS - similar to TTP, less CNS, more renal (child w E Coli 0157:H7); age 6 mo-4yo;

Question 13

Treatment of Hemolytic Uremic Syndrome

Answer 13

Tx: supportive care and admit; plasma exchange, Abx may worsen; dialysis if renal failure
-avoid plts

Question 14

What is the pathophysiology of Hemophilia A -

Answer 14

Hemophilia A - ↓VIII, prolong PTT

Question 15

What is the treatment of Hemophilia A?

Answer 15

Tx : recomb VIII, VIII conc: Mild bleeding (hematuria, early hemarthrosis, laceration) 12.5 units/kg, Moderate (oral lacerations, dental, late hemarthrosis) 25 units/kg,
severe (CNS, GI, major trauma/surgery) 50 units/kg. Each unit/kg increases plasma factor VIII level by 2%
-Cryo if no recombinant VIII- one bag has 80-100 units of factor VIII
-FFP increases by 3-5%- limited use
-DDAVP for acute bleeding or prophylaxis (0.3mcg/kg/dose IV)
-Ice, compression, and splinting
-Consult Heme

Question 16

Pathophysiology of Von Willebrand’s Dz -

Answer 16

Von Willebrand’s Dz - ↓VIII:vwf (need for plt adhesion and causes plt malfunction) (also ↓VIII) nl PT, PTT but bleeding time increased; most common hereditary
blood d/o.
Type 1 (decreased vWF), type II (abnormal or dysfunctional vWF), type III (no vWF)

Question 17

Treatment of Von Willebrand’s Dz-

Answer 17

Tx : DDAVP 0.3mcg/kg
-Humate P- factor VIII conc
-Cryo- 10 units/kg
-FFP- limited use due to volume overload

Question 18

Pathophysiology of Hemophilia B (Xmas Dz) -

Answer 18

Hemophilia B (Xmas Dz) - ↓IX, sex linked; Inc PTT, nl PT

Question 19

Treatment of Hemophilia B (Xmas Dz)-

Answer 19

Tx : recomb IX or IX conc : minor 25 units/kg, moderate 50 units/kg, severe 100 units/kg. Increases activity by 1%
-FFP if no recomb IX

Question 20

Pathophysiology of DIC -

Answer 20

DIC - ↓plt, schistocytes, ↑PT/PTT/TT, ↓fibrinogen, ↑or↓ D-dimer, inc FSP.
1. Thrombin generation, small vessel thrombosis and consumption of clotting factors and platelets.
2. Concomitant activation of fibrinolytic system–>breakdown of fibrin clots and subsequent bleeding
Trigger → loss of localization or compensated control in the intravascular activation of coagulation

Question 21

Causes of DIC-

Answer 21

Causes: Sepsis (most common), leukemia, carcinoma, trauma, pancreatitis, liver disease, pregnancy, snake bite, ARDS, transfusion, transplant

Question 22

DIC Clinical Findings-

Answer 22

Clinical findings:
Sepsis: hypercoagulation may predominate (cutaneous gangrene, thrombotic purpura)
Inflammation induces synthesis of fibrinogen→ normal or elevated levels of fibrinogen→ more hypercoagulable
Avoid blood products unless bleeding, purpura fulminans may require plasma exchange
Leukemia: hyperfibrinolysis (petechiae, ecchymosis, oozing, hematuria)
Trauma/OB: hypercoagulation and hyperfibrinolysis (major bleeding complications)
Some maybe subclinical

Question 23

DIC Lab Findings:

Answer 23

Lab findings:
Thrombocytopenia (Most common), prolonged PT, low fibrinogen, elevated D dimer
Tx: tx underlying cause (infx, obstetric pathology, trauma, malignancy, drugs, transfusion) and predominant sx

Question 24

DIC Treatment:

Answer 24

Question 25

Warfarin

Answer 25

Warfarin
Inhibits Vitamin K epoxide reductase → limiting the synthesis of factors II, VII, IX, X, protein C and S
Vitamin K: all active bleeding should get 5-10 mg IV slow, onset 2-6 hours with effective response at 24 hrs
Anaphylactic reactions 3/10,000 due to diluent
FFP: contains all coagulation factors (AB is universal donor), needs 15-20 min to thaw, may need 10-15m L/kg for serious bleeds
For intracranial start with 2 units, for extracranial 4 units- 1 unit corrects clotting factors by 2.5-5%
PCC4: activated factor VII, non activated II, IX, X, also Protein C and S with heparin and AT3
Indicated for acute major bleeding. Dosing depends on INR and weight, 25-50 IU/kg
Contraindicated in DIC and HIT → thromboembolic events
Quicker, costs more, faster time to INR reversal

Question 26

INR Reversal-

Answer 26

Question 27

Heparin-

Answer 27

Heparin
Heparin joins AT3 → binds factor II and X→ blocking cascade
Protamine sulfate (sperm of salmon)- binds and inactivates heparin: 1 mg/100 units of heparin

Question 28

Low molecular weight heparin-

Answer 28

Low molecular weight heparin
Joinds with AT3→ binds factor II and X (binds X more than heparin)
Protamine has some effect on LMWH, can try rVIIa

Question 29

Direct thrombin inhibitors-

Answer 29

Direct thrombin inhibitors: Dabigatran (Pradaxa)
Inhibitors of free thrombin and clot- bound thrombin
Idarucizumab (praxbind): 5 g IV provided as 2 separate vials
FFP and PCC4 minimal improvement

Question 30

Direct Xa inhibitors:

Answer 30

Direct Xa inhibitors: Rivaroxaban (Xarelto), Apixaban (Eliquis), Fondaparinux (Arixtra)
Inhibit Xa (first step in common pathway). Xarelto and Eliquis directly bind, Arixtra binds AT3
PCC4 has potential role for xarelto
Specific reversal agent in development: Adexanet Alfa
Recombinant factor VIIa has shown increased risk of arterial thromboembolism

Question 31

Platelet inhibitors-

Answer 31

Platelet inhibitors: Clopidogrel
Blocks platelet aggregation and degranulate
Tx: platelets, DDAVP, rVIIa

Question 32

Thrombolytics-

Answer 32

Thrombolytics
Catalyze plasminogen to plasmin→ clot lysis
Aminocaproic acid- blocks fibrinolysis by reversibly blocking plasminogen. Used in bleeding patients with hemophilia
Cryoprecipitate- contains fibrinogen