Coagulopathies Flashcards
Idiopathic Thrombocytopenic Purpura (ITP) definition
- Autoimmune: B cells produce IgG antibodies, directed against platelet membrane, increase platelet destruction, inhibit platelet production
- isolated thrombocytopenia
- no apparent associated conditions
ITP Classifications (4)
- Primary: no identifiable underlying cause
- Secondary: immune mediated and associated with underlying disorder
- Chronic: lasting longer than 12 months
- Refractory: failure to respond, relapse occurs after splenectomy
Incidence of ITP
- Children: self limiting and usually caused by viral illness, results in bruising and mucosal bleeding
- adults: chronic, requires periodic tx
- More common in women (ages 20-40) than men 2:1
- Common secondary manifestation to systemijc lupus and CLL
What may induce thrombocytopenia in ITP
Heparin (most common in hospital setting) Sulfonamides Thiazides Quinine Gold Cimetidine
S&S of ITP
- Mucosal or epidermal bleeding (epistaxis, oral bleeding, menorrhagia, purpura, petechiae)
- Patient usually systemically well, afebrile, no abnormal findings besides bleeding
Hallmark lab finding for ITP
Thrombocytopenia, <20,000 platelets, platelets are enlarged (megathrombocyte)
Evans Syndrome
coexistent dz with ITP in 10% of cases
-Anemia, retics, and spherocytes on peripheral smear
Most sensitive and specific antibody test for ITP
Monoclonal antibody immobilization of platelet antigens
-IgG platelet antibodies present in 90% of patients
Ig
Bone marrow findings ITP
normal or increased megakaryocytes
ITP tx
- Prednisone, bleeding diminishes within a day and platelets rise within a week
- High dose IV gamma globin: very expensive and usually used in emergency, Used in HIV patients instead of steroids
- Splenectomy: used when prednisone fails, give Pneumococcal vaccine weeks before to minimize complications
- Chemotherapy: done after prednisone and spleen removal don’t work, Danazol or immunosuppressive agents (vincristine, vinblastine, azathioprine, cyclophosphamide)
- Thrombopoiesis stimulating agents
- Platelet transfusion in life threatening instance
- WinRho therapy
WinRho therapy or anti D antibody therapy
Only for Rh positive individuals born to Rh negative mothers.
-concentrated antibodies that bind to the Rh antigen on RBCs, helps increase platelet count but may cause anemia
most serious complication of ITP
Spontaneous intracranial hemorrhage
-less than 1% affected
at risk when platelets drop <5000
Heparin induced Thrombocytopenia (HIT) definition
Thrombocytopenia induced by heparin
Produces arterial and venous thrombosis
Functional HIT
fall in platelet count 1-4 days after starting heparin. returns to normal after heparin discontinued (most common)
Immunologic HIT
fall in platelet count within 5-10 days from starting heparin, immune mediated disorder, higher incidence of thromboembolic event
Antibody formation HIT
IgG autoantibody formation against heparin platelet factor 4 complex
incidence/predisposing factors for HIT
- most common type of drug induced thrombocytopenia
- most common form of thrombocytopenia in the hospital
- occurs more with unfractionated heparin than LMWH
- more common in surgical patients due to need for DVT/VTE prophylaxis and loading dose heparin
S&S of HIT
- Asymptomatic at first
- symptoms related to location of thromboses
- skin necrosis at injection site
- anaphylactic reaction
Platelet labs suggesting HIT
Suspect if platelets drop >50% even if there is no thrombocytopenia
HIT tests (4)
- Heparin induced platelet aggregation assay: 90% sensitivity and 100% specificity
- Serotonin release assay: done with above test as standard
- Platelet C serotonin release assay: 94%sensitive and 100% specific but difficult and time consuming
- Heparin PF4 enzyme liked immonosorbent assay: immunologic test for heparin induced antibodies
4 Ts for clinical probability of HIT
The extent of thrombocytopenia
Timing of thrombocytopenia
Presence of thrombosis
Thrombocytopenia
score of 4 or higher indicates intermediate to high risk of HIT
HIT tx
- hematology consult
- Stop heparin
- give direct thrombin inhibitors as alternative anticoagulation: danaparoid (check renal function), argatroban (check liver function), Bivalirudin, Fondaparinux (check creatinine clearance, MUST be > 30ml/min)
-Transition to comadin when INR at goal of 2-3, platelet count has increased to over 150,000. Start with less than 5 mg per day. Minimum of 5 days of overlapping before discontinuing thrombin inhibitor
Disseminated Intravascular Coagulation (DIC) definition
- acquired coagulation disorder with hemorrhage and thrombosis that occurs as a secondary process concomitant with a pathophysiologic dz or clinical state
- caused by consumption of many coagulation factors and platelets
- an abnormal stimulus results in the formation of excess thrombin which causes: fibrinogen consumption, irreversible platelet aggregation, activation of the fibrinolytic system
incidence/predisposing factors of DIC
- most common cause is infection (10-20% gram negative sepsis)
- other causes: ob complications, cancer, liver dz, trauma, burns, transfusion of ABO incompatible RBCs
S&S of DIC
- Bleeding: oozing from previously punctured sites, from multiple sites
- sites could be oral, gingival, GI, GU
- Acute DIC: tachycardia, hypotension, edema
- VTE, spontaneous bruising, skin necrosis
- Thrombosis can be superficial or deep, digital ischemia or gangrene may be the most common form, most common in pts with cancer
Labs for acute DIC
- no single lab is diagnostic
- platelets <150,000
- PT and PTT prolonged by 70% and 50%
- Fibringoen, factor V, and factor VII levels are low
- fragmented RBCs (schistocytes) on blood smear
- Diagnosis confirmed with rapidly falling fibrinogen levels on repeat testing
Subacute DIC labs
PT and PTT normal
Fibrinogen levels normal
Thrombocytopenia and elevated D dimer
Chronic or compensated DIC labs
-Elevated fibrin degradation product levels >45, d dimer positive at greater than 1:8 dilution
DIC tx
- Hematology consult
- Correct underlying cause: hypotension, sepsis, ob issues
- Transfuse PRBCs, platelets (goal 30,000-50,000), cryoprecipitate (goal fibrinogen 150 mg/dl), FFP every 30 minutes
- 1 unit cryoprecipitate increases fibrinogen level by 6-8mg/ml; 15 units raises level from 50-150 mg/dl
- Prevent hypoxemia
- HEparin therapy if thrombosis but test antithrombin III levels b/c heparin won’t be effective if antithrombin depleted
Thrombotic thrombocytopenic purpura (TTP) what is it
thrombocytopenia due to the incorporation of platelets into thrombi in the microvasculature and microangiopathic hemolytic anemia, which results from shearing of erythrocytes in fibrin networks in the microcirculation
autoantibodies against ADAMTS-13 aka von Willebrand factor cleaving protease, lead to accumulation of huge von willebrand factor multimers…leading to vessel obstruction and organ dysfunction
presentation of TTP patients
affects adults severe thrombocytopenia fever typical but mild kidney dz Decreased activity of ADAMTS-13, inhibitor usually identified
Initial Management for TTP
Mortality 95% without tx
TPE :plasma exchange, everyday until LD and platelet count normal for 2 days
hemodialyis for severe renal impairment
Platelet transfusions contraindicated unless TPE underway
Secondary tx of TTP not responding to 1st line tx
Rituximab, corticosteroids, IVIG, vincristine, cyclophosphamide ans splenectomy
