22 - Platelet Disorders Flashcards
1
A
- Cytoplasmic fragments derived from megakaryocytes
- Participate in (primary) hemostasis through interactions with von Willebrand factor (GP1b) and fibrinogen (GPIIb/IIIa)
- Normal platelet counts range from 150,000 – 400,000/μL
- Approximately one-third of circulating platelets are
normally sequestered in the spleen
2
Q
Platelets and Bleeding
A
- Thrombocytopenia – platelet count below 150,000/μL, but…
- Platelet counts > 50,000/μL not associated with
clinical bleeding (unless coexistent functional defect) - Clinically significant “spontaneous” bleeding occurs with platelet counts below 10,000/μL
- Platelet bleeding typically manifests as more superficial skin and mucous bleeding (petechiae, epistaxis, menorrhagia, etc.)
3
Q
Thrombocytopenia
A
- Mechanisms
- Decreased production (aplastic anemia, marrow infiltration, marrow suppression)
- Ineffective production (megaloblastic anemia, myelodysplasia)
- Increased destruction/consumption (immune versus
non-immune) - Increased sequestration (splenomegaly)
- Hemodilution (transfusion)
- Pseudothrombocytopenia (platelet clumping)
4
Q
Pseudothrombocytopenia
A
- Artifactual decrease in platelet count
- Inadequate anticoagulant/mixing
- EDTA-dependent agglutinins (0.1% of patients)
- Cold platelet agglutinins
- Redraw draw sample in sodium citrate tube
- May appear as platelet clumps or platelet satellitism
5
Q
Idiopathic/Immune Thrombocytopenia (ITP)
A
- Auto-immune
- IgG auto-antibodies to platelets/megakaryocytes
- Increased destruction by (splenic) macrophages
- T cell-mediated destruction
- Idiopathic or secondary to autoimmune disease
(lupus), lymphoma, infections (HIV), drugs
6
Q
ITP - Clinical
A
- Females > males
- Children – self-limited, post viral infection
- Adults – chronic, relapsing
- Isolated thrombocytopenia
- IgG anti-platelet antibodies detected (80% patients)
7
Q
ITP - Morphology
A
- Thrombocytopenia with large platelets
- Normal to increased megakaryocytes in bone marrow
8
Q
ITP - Management
A
- Conservative (especially children)
- First-line
- Corticosteroids (80% response)
- Intravenous immunoglobulin (IVIg)
- Second-line – rituximab, romiplostim, eltrombopag,
fostamatinib, splenectomy - Third-line – chemotherapy, stem cell transplant
9
Q
Heparin-Induced Thrombocytopenia (HIT) - Non-immune (type I)
A
- Non-immune (type I)
- Common (10-30% of patients receiving heparin)
- Heparin directly binds to platelets causing mild activation
- Develop within 5 days of starting heparin
- Mild thrombocytopenia (80-100K)
- Spontaneous recovery despite continued heparin
- Usually clinically insignificant
10
Q
Heparin-Induced Thrombocytopenia (HIT) - Immune (type II)
A
- Immune (type II)
- Heparin binds to platelet factor 4 (PF4)
- IgG antibodies against heparin-PF4 complexes,
which bind to and activate platelets (thrombosis) - Destruction of platelets by splenic macrophages
(thrombocytopenia)
11
Q
Immune HIT – Clinical Features
A
- Unfractionated heparin > low molecular weight heparin
- Decrease in platelet count by >50% from the highest value after heparin is started
- Develops 5-10 days after starting heparin (can be
earlier with previous exposure) - Moderate thrombocytopenia (50-80K)
- Associated with venous thrombosis (50%) or arterial
thrombosis (less common)
12
Q
Immune HIT - Management
A
- Discontinue all heparin
- Still a risk for thrombotic events, so…
- Anticoagulation with non-heparin agent
- Direct thrombin inhibitors (argatroban, bivalirudin,
dabigatran - Factor Xa inhibitors (apixaban, rivaroxaban,
fondaparinux)
13
Q
Drug-Induced Thrombocytopenia
A
- Over 300 drugs have been implicated
- Immune and non-immune mechanisms
- Diagnostic criteria
- Exposure to the drug preceded thrombocytopenia
- Recovery with discontinuation of the drug
- Candidate drug was the only drug used
- Other causes are excluded
- Re-exposure causes recurrent thrombocytopenia
14
Q
Drug-Induced Thrombocytopenia
- Management
A
- Discontinue the offending drug(s)
- With multiple possible drugs, stop all recently-
started drugs (especially antibiotics) and restart as needed - Expect recovery after 4-5 half-lives of the drug
15
Q
Other Immune Thrombocytopenia
A
- Neonatal allo-immune thrombocytopenia
- Maternal antibodies cross placenta and cause
destruction of fetal platelets - Post-transfusion purpura
- Allo-immune antibodies secondary to prior transfusion with platelets
- Most common target is HPA-a1 antigen (glycoprotein
IIIa/CD61)
16
Q
Thrombotic Thrombocytopenic Purpura (TTP)
A
- First described in 1924 by Eli Moschcowitz
- Deficiency of ADAMTS13 (vWF cleaving enzyme)
- Ultra-large vWF multimers accumulate and activate platelets
- Systemic microvascular platelet thrombi
- Inherited or acquired
- Gene mutations
- Drug-induced (clopidogrel)
- Auto-immune disease
- Infections
- Pregnancy
- Malignancy
18
Q
TTP - Morphology
A
22
Q
Bernard-Soulier Syndrome
A
- Autosomal recessive inheritance
- Defective GPIb receptor on platelets
- Abnormal binding to vWF (impaired platelet adhesion)
- Mild thrombocytopenia with large platelets, prolonged bleeding time, abnormal ristocetin-induced platelet aggregation
- Variable clinical severity
23
Q
Glanzmann Thrombasthenia
A
- Autosomal recessive inheritance
- Defective GPIIb/IIIa receptor on platelets
- Abnormal binding to fibrinogen (impaired platelet
aggregation), abnormal clot retraction - Normal platelet count, prolonged bleeding time,
abnormal platelet aggregation (except ristocetin) - Variable clinical severity
24
Q
Storage Pool Disorders
A
- Group of related disorders, variable inheritance
- Abnormal platelet granules/secretion (impaired
aggregation) - Normal platelet count, pale/hypogranular platelets,
prolonged bleeding time, abnormal platelet
aggregation (primary wave only, disaggregation) - Variable clinical severity
