SM_254b: Thrombocytopenias Flashcards
Primary hemostasis is ____ and ____
Primary hemostasis is binding to vWF and collagen and platelet plug formation
Secondary hemostasis provides the co-factors ____ and ____ to the coagulation cascade factors
Secondary hemostasis provides the co-factors phospholipid and calcium to the coagulation cascade factors
Platelets are produced in the ____ from ____
Platelets are produced in the bone marrow from megakaryocytes
Platelet production is mediated by ___
Platelet production is mediated by thrombopoietin
- Constitutively produced by liver
- Removed from circulation by binding to platelets
Thrombocytopenia can result from ___, ___, ___, or ___
Thrombocytopenia can result from lack of production, destruction, redistribution, or congenital disorder
Describe an algorithm for thrombocytopenia evaluation
Algorithm for thrombocytopenia evaluation
Isolated thrombocytopenia, normal blood smear, and increased megakaryocytes on bone marrow biopsy should make you think of ____
Isolated thrombocytopenia, normal blood smear, and increased megakaryocytes on bone marrow biopsy should make you think of immune thrombocytopenia purpura
Describe types of thrombocytopenia
Thrombocytopenia
- Mild (100,000-149,000/uL): minimal bleeding risk
- Moderate (50,000-99,000/uL): minimal risk of spontaneous bleeding, may have bleeding with trauma and invasive procedures
- Severe (< 50,000/uL): may have spontaneous bleeding especially <20,000/uL, bruising or petechiae are likely and common
Immune thrombocytopenia purpura involves ___
Immune thrombocytopenia purpura involves auto-antibody mediated platelet destruction (usually against GP IIb/IIIa)
___, ___, ___, and ___ cause secondary immune thrombocytopenia purpura
Lupus, malignancy, HIV, and hepatitis C cause secondary immune thrombocytopenia purpura
Describe the time course of immune thrombocytopenia purpura
Time course of immune thrombocytopenia purpura: duration of platelet count < 100,000 uL
- Acute / newly diagnosed: < 3 months from diagnosis
- Persistent: 3-12 months from diagnosis
- Chronic: > 12 months from diagnosis
Immune thrombocytopenia purpura is treated with ____, ____, ____, ____, and ____
Immune thrombocytopenia purpura is treated with
- Steroids
- IV Ig
- Rituximab
- Tpo receptor agonists
- Splenectomy
Describe immune thrombocytopenia in kids
Immune thrombocytopenia in kids
- Usually preceded by viral illness: 3-30 days prior
- Self-limited disease
- Bleeding is rare even if platelet count < 20,000/uL
- Treatment can improve platelet count in 1-4 days
Describe immune thrombocytopenia in adults
Immune thrombocytopenia in adults
- Usually occurs absent preceding infection
- Treatment generally recommended if platelet count < 30,000/uL, considerations for bleeding symptoms and comorbid conditions
- High relapse rates
Immune thrombocytopenia purpura involves ____
Immune thrombocytopenia purpura involves antibody-mediated destruction within the reticuloendothelial system
- Physiologic consumption: localized or generalized infections or bleeding
- Occurs because platelet activation is the first step of platelet death
Describe mechanisms of platelet destruction
Mechanisms of platelet destruction
- Other antibody-mediated destruction: heparin-induced thrombocytopenia, drug-induced thrombocytopenia, and infection-related thrombocytopenia
- Thrombotic microangiopathies: disseminated intravascular coagulation, thrombotic thrombocytopenia purpura, hemolytic uremic syndrome, HELLP
Heparin-induced thrombocytopenia occurs when ____
Heparin-induced thrombocytopenia occurs when heparin and platelet factor 4 form a neoepitope against which IgG antibodies are made
Patient on heparin, with new or worse thrombosis since onset of thrombocytopenia, and isolated thrombocytopenia with normal coags has ____
Patient on heparin, with new or worse thrombosis since onset of thrombocytopenia, and isolated thrombocytopenia with normal coags has heparin-induced thrombocytopenia
Recent heparin use can ___, indicative of heparin-induced thrombocytopenis
Recent heparin use can shorten time between heparin initiation and onset of thrombocytopenia, indicative of heparin-induced thrombocytopenia
- 5-14 days
Patient taking heparin with reduction of platelet count by 50% from pre-heparin count has ___
Patient taking heparin with reduction of platelet count by 50% from pre-heparin count has heparin-induced thrombocytopenia
- Does not technically need to be thrombocytopenic
Heparin-induced thrombocytopenia is treated by ____
Heparin-induced thrombocytopenia is treated by discontinuing heparin
- Treat with alternative anticoagulation
Describe thrombotic microangiopathies
Thrombotic microangiopathies
- Thrombosis in microvessels: usually capillaries and arterioles
- Caused by endothelial activation or damage
- General term encompassing multiple diseases
Thrombotic thrombocytopenia purpura involves ____, ____, ____, ____, and ____
Thrombotic thrombocytopenia purpura involves thrombocytopenia, fever, altered mental status, hemolytic anemia, and renal failure
Thrombocytopenia, intravascular hemolysis, renal failure, fever, and neurologic symptoms is ____
Thrombocytopenia, intravascular hemolysis, renal failure, fever, and neurologic symptoms is thrombotic thrombocytopenia purpura
Melanin can mask ____ and ____
Melanin can mask petechiae and purpura
Describe pancytopenia physical exam findings
Pancytopenia
- Pallor on conjunctiva, palms, soles, nailbeds, gingiva, and tongue
- Some with anemia can appear to have jaundice
Low platelets, WBC, RBC, and mean cell volume is ___
Low platelets, WBC, RBC, and mean cell volume is pancytopenia
Hypocellular bone marrow biopsy indicates ___
Hypocellular bone marrow biopsy indicates decreased platelet production
Lack of production of platelets in bone marrow can result from ___ or ___
Lack of production of platelets in bone marrow can result from aplasia or myelophthisis
Describe aplasia
Aplasia (lack of production)
- Primary bone marrow failure: aplastic anemia, myelodysplasia
- Secondary bone marrow suppression: cytotoxic medications (chemo) or radiation, viral infection
Drugs and infections can cause immune-mediated and hypoproliferative thrombocytopenia
Describe myelophthisis
Myelophthisis (lack of production)
- Cancer: leukemia, metastatic
- Myelofibrosis
- Osteopetrosis
Liver failure can cause ____
Liver failure can cause lack of platelet production
Insufficient nutrients such as ____, ____, and ____ may cause lack of platelet production
Insufficient nutrients such as Vitamin B12, folate, and copper may cause lack of platelet production
Platelet redistribution involves ____ and ____
Platelet redistribution involves sequestration and dilution
- Sequestration: platelets are in the body but not circulating in the bloodstream
- Dilution: platelet count is measured in platelets/uL so increased volume will lead to decreased platelets/uL
Describe platelet sequestration
Platelet sequestration
- In spleen
- Splenomegaly: porrtal hypertension, infiltrative processes (lymphoma), infection (mono), splenic sequestration crisis in patients with HbSS or HbSC
- Mild to moderate thrombocytopenia
- If platelet count is < 75,000/uL look for another etiology
Describe platelet dilution
Platelet dilution
- Pregnancy: increased blood volume, same rate of platelet production
- Massive fluid resuscitation: massive transfusion that does not include platelets, large amounts of crystalloid fluids
Describe causes of thrombocytopenia in neonates
Thrombocytopenia in neonates
- Antibody-mediated: alloantibody immune thrombocytopenia, passive anti-platelet antibodies
- Congenital platelet disorder: Bernard Soulier, Wiscott Aldrich syndrome
Describe Glanzmann thrombasthenia
Glanzmann thrombasthenia
- Not thrombocytopenia but is congenital
- Platelet count and morphology are normal
- Platelets are dysfunctional due to lack of GP IIb/IIIa (binds fibrinogen)
- Bleeding symptoms are moderate to severe
Describe Bernard Soulier syndrome
Bernard Soulier syndrome
- Large platelets (macrothrombocytopenia)
- Defect in GP Ib-V-IX (vWF receptor and part of platelet cytoskeleton)
- Autosomal recessive
- Moderate to severe bleeding
Describe Wiscott Aldrich syndrome
Wiscott Aldrich syndrome
- Small platelets (microthrombocytopenia)
- Defect in WAS gene (WASp protein)
- X-linked recessive
- Immune deficiency, eczema, microthrombocytopenia
