Platelets -H/O Flashcards
Mechanisms of Thrombocytopenia
- Decreased Production
- Bone marrow failure (aplastic anemia, MDS, inherited marrow failure states)
- Marrow replacement (leukemia, lymphoma, metabolic disorders)
- Marrow toxins (drugs, radiation, ethanol)
- Nutritional deficiency (B12, folic acid) - Increased Destruction / Consumption
- Immunologic (drugs, HIT, ITP)
- Non Immunologic (DIC, TTP/HUS) - Hypersplenism
Drug Induced Thrombocytopenia
-can directly affect the marrow
OR
-can have antibodies directed against drug/platelet complex or drug induced antibody response
Tx-stop offending drug
HIT
- Immune response directed against heparin / platelet factor 4 complexes
- Anti-Hep/PF4 IgG binds to platelet Fc receptors, resulting in platelet activation and generation of microparticles and thrombin
- Thrombocytopenia begins 5 - 10 days after initiation of heparin exposure (may occur sooner in patients with recent exposure and residual antibodies)
- More than 50% decrease from baseline platelet count or absolute thrombocytopenia
- Absence of other causes of thrombocytopenia
- ANY form of heparin can precipitate HIT (although less common with low MW heparins)
- Confirmation by lab testing
- Return to normal platelet count when heparin is discontinued
- Venous and / or arterial thrombosis occurs in 30 - 50% - 10% require limb amputation, 20% mortality
Immune Thrombocytopenic Purpura (ITP)
- Loss of tolerance to self
- IGG antibody against glycoprotein IIb/IIIa, Ib/IX
- Cytokines, abnormal T cells…
- Autoantibodies that bind to platelets and accelerate their clearance by the spleen
- ITP is a diagnosis of exclusion
- Most common cause of thrombocytopenia in childhood, adolescence and young adults
Childhood ITP:
-Acute onset, often after viral illness
-Often resolves spontaneously within days or weeks
>90% resolve 1-2 years after dx
Adult ITP:
- Insidious onset (most have symptoms for > 2 months)
- Rarely resolves spontaneously
- May patients go on to have chronic ITP
Clinical Features of ITP
- Most adults have symptoms for > 2 months, children have symptoms for a day or two
- Most children have no associated health issues
- Most adults have other associated medical issues – autoimmune disorders, malignancy, etc.
- Petechiae in dependent regions
- Echymosis
- Menorrhagia, epistaxis, gingival bleeding, blood in stool or urine
- Otherwise healthy
- No lymphadenopathy or splenomegaly
Laboratory Features of ITP
- Severe thrombocytopenia (platelets < 10,000)
- In adults or in patients with more insidious onset platelet count may be in range of 20-60,000.
- CBC otherwise normal, MPV high
- Peripheral smear may show large platelets
- Normal coagulation times (PT/INR, PTT) and fibrinogen
- Normal/increased megakaryocytes in bone marrow
- Platelet antibody tests are rarely helpful
Treatment of ITP
ADULTS
- Steroids
- IVIG
- WinRho
- Rituxan
- Splenectomy
- Observation
Children
- Observation – 75%
- IVIG
- WinRho
- Steroids
- Rituxan
- Splenectomy
Disseminated Intravascular Coagulation
DIC
- Life-threatening coagulation disorder caused by excessive activation of coagulation system that overwhelms natural anticoagulant mechanisms
- Microvascular thrombi cause widespread tissue ischemia and multiple organ dysfunction
- Bleeding due to consumption of platelets and plasma clotting factors
- Thrombocytopenia
- Prolonged coagulation times (PT/INR, PTT)
- Low fibrinogen, other coagulation factors also low
- Schistocytes on blood smear
- VERY ILL appearing
Disseminated Intravascular Coagulation
(DIC) - causes/tx
Causes -Infection / sepsis -Malignancy -Obstetrical catastrophes (abruption placenta, amniotic fluid embolism, retained tissue) -Severe tissue injury (trauma, burns) Tx -Treat the underlying cause -Transfuse platelets, FFP, cryoprecipitate as needed -Consider low dose heparin
Classification of thrombotic thrombocytopenic purpura (TTP)
- Idiopathic
- Secondary
- Pregnancy
- Autoimmune disease (SLE, scleroderma)
- Drug toxicity (chemotherapy, CSA, ticlopidine)
- HIV infection
- Bone marrow transplant
- Malignancy - Familial
Classic Pentad of TTP
- Thrombocytopenia
- Microangiopathic hemolytic anemia
- Neurologic symptoms
- Renal dysfunction
- Fever
- If you wait for the entire pentad to develop, you have waited too long !
Diagnosis of TTP
- High index of clinical suspicion
- Hemolysis + Thrombocytopenia = TTP, DIC…
- Coagulation times should be normal, or only slightly prolonged
- Examination of the peripheral blood smear is absolutely essential !
- ADAMST 13 level
Treatment of TTP
- Treatment must be started promptly
- Plasma exchange has been the main treatment modality since the early 1980s
- Prior to the use of plasma exchange, the mortality rate for TTP was 90%
- With prompt diagnosis and treatment, 90% of patients now survive
Hemolytic uremic syndrome
- Seen primarily in children
- Predominantly renal symptoms, anemia and thrombocytopenia
- Associated with infections with E coli or Shigella dysenteriae
- Patients often require dialysis
- Therapy is generally supportive
HIT summary
- Heparin exposure
- Platelets drop more than 50% from baseline
- Variable INR, PTT, Fibrinogen
- Life- and limb-threatening