DIC/anticoagulation reversal Flashcards
What is the Pathophysiology of HIT?
HIT - thrombocytopenia but causes thrombotic problems, occurs w LMWH too; usually in 1st week
What are the findings in HIT?
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
What is the treatment for HIT?
Tx : stop heparin/LMWH; start alternative anticoagulant ( lepirudin, bivalirudin or argatroban), reverse warfarin. Avoid warfarin and avoid platelet transfusions
Presentation of TTP-
10-40 yo female, thrombocytopenia, microangiopathic hemolytic anemia (schistocytes, frag RBC’s), fluctuating neuro sx, renal dz, fever.
Findings in TTP-
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
Treatment of TTP-
Tx: Steroids, dialysis if renal failure, Plasma exchange dramatically ↓ mortality, FFP (gives back ADAMTS13)
-avoid plts
Presentation of ITP?
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
Treatment of Acute ITP?
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
Treatment of Acute Pediatric ITP?
Pediatrics: controversial, usually self resolves, consider if concern for ICH- need to discuss with hematologist
Treatment of Chronic ITP?
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
Treatment of ITP in pregnancy?
Pregnancy: count should be maintained > 30,000 and 50,000 near term
Presentation of Hemolytic Uremic Syndrome
HUS - similar to TTP, less CNS, more renal (child w E Coli 0157:H7); age 6 mo-4yo;
Treatment of Hemolytic Uremic Syndrome
Tx: supportive care and admit; plasma exchange, Abx may worsen; dialysis if renal failure
-avoid plts
What is the pathophysiology of Hemophilia A -
Hemophilia A - ↓VIII, prolong PTT
What is the treatment of Hemophilia A?
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
Pathophysiology of Von Willebrand’s Dz -
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)
Treatment of Von Willebrand’s Dz-
Tx : DDAVP 0.3mcg/kg
-Humate P- factor VIII conc
-Cryo- 10 units/kg
-FFP- limited use due to volume overload
Pathophysiology of Hemophilia B (Xmas Dz) -
Hemophilia B (Xmas Dz) - ↓IX, sex linked; Inc PTT, nl PT
Treatment of Hemophilia B (Xmas Dz)-
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
Pathophysiology of DIC -
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
Causes of DIC-
Causes: Sepsis (most common), leukemia, carcinoma, trauma, pancreatitis, liver disease, pregnancy, snake bite, ARDS, transfusion, transplant
DIC Clinical Findings-
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
DIC Lab Findings:
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
DIC Treatment:
Warfarin
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
INR Reversal-
Heparin-
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
Low molecular weight heparin-
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
Direct thrombin inhibitors-
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
Direct Xa inhibitors:
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
Platelet inhibitors-
Platelet inhibitors: Clopidogrel
Blocks platelet aggregation and degranulate
Tx: platelets, DDAVP, rVIIa
Thrombolytics-
Thrombolytics
Catalyze plasminogen to plasmin→ clot lysis
Aminocaproic acid- blocks fibrinolysis by reversibly blocking plasminogen. Used in bleeding patients with hemophilia
Cryoprecipitate- contains fibrinogen
