W5 LECT3 Flashcards
Name 2 broad classes of platelet disoders
- Quantitative disoders
- Qualitative disoders
Name 2 types of Platelet quantitative disoder
- ITP
- TTP
Name 2 types of platelet qualitative disoders
- Glanzmann Thrombosthenia (Aggregation)
- Bernard-Soulier Syndrome (Adhesion)
T/F:
All platelet disoders, no matter quantitative or qualitative, are either acquired or inherited
TRUE
Increased platelet consumption through formation of thrombus lead to what qualitative platelet disoder?
Thrombotic thrombocytopenic pupura
Increased platelet consumption due to antibody mediated destruction to platelet lead to what qualitative platelet disoder?
Immune thrombocytopenic Pupura (ITP)
Discuss the pathogenesis of ITP
1951 – Antibodies directed against platelet glycoproteins
*Immune Thrombocytopenic Purpura excluded for the 1st time
- Antiplatelet antibodies directed against platelet specific glycoproteins»opsonised platelets destroyed in the spleen»_space;shortened platelet half-life
- 1980’s – In addition to increased platelet clearance, also decreased platelet production
Name 3 causes of thrombocytopenia
- Decreased platelet production
- Increased platelet consumption
- Platelet sequestration by the spleen
What are the clinical presentations of ITP?
- Primary
*Children (1 – 5 years of age)
*Platelet count <30 x 109/L
*Generally preceding viral infection - Secondary
*Lymphoproliferative neoplasm
*Infections: Viral (HIV, EBV, CMV, Hepatitis)
*Autoimmune disorders - Acute (newly diagnosed): ITP duration <3 months
- Persistent: ITP duration 3 – 12 months
- Chronic: ITP duration >12 months
- Mucocutaneous bleeding
May 2024 NHLS-University of the Witwatersrand 8
Discuss the management of ITP
- First Line Therapy
*Corticosteroids (CS)
*IV Immunoglobulin (IVIG) – used with CS when a more rapid
increase in platelet count is required
*Either IVIG or Anti-D (in appropriate patients) if CS contra-
indicated - Second Line Therapy
*Rituximab (anti-CD 20 monoclonal antibody)
*Thrombopoietin Receptor Agonists (TPO-RA)
*Splenectomy
How to carry out ITP investigations?
- FBC
-Thrombocytopenia (platelet count <30 109/L)
-Platelet morphology: typically normal, with varying numbers of large platelets - Exclude secondary causes:
* Liver function test
* Thyroid function test
* Haematinics: Vitamin B12 and folate
* Infections
* Viral screen: HIV, Hepatitis B/C, CMV, EBV
* Bacterial: Cultures (if clinically appropriate)
* Malaria screen
* Mycobacterial (TB), etc
* Coagulation screen: PT, aPTT, D-dimers
* Autoimmune: ANA, Rheumatoid factor, ACLA, Lupus anticoagulant
* Clinical examination and Imaging to assess spleen size - Bone Marrow investigation: exclude other causes, normal / increased megakaryocytes
A qualitative platelet disoder that falls under the category of Thrombotic Microangiopathies (TMA)
* DIC, HUS, aHUS, HELLP
TTP
Haematological Emergency
TTP
Characterised by low platelets with micro-angiopathic
haemolytic anaemia
TTP
To see o the peripheral blood picture of Thrombotic Microangiopathies
schistocytes- RED CELL FRAGMENTS
Aetiology of TTP
- Inherited / Congenital:
* Very rare
* Severe deficiency of ADAMTS13 (metalloprotease with
thrombospondin repeats) - Acquired:
* Idiopathic
* HIV
* Pregnancy
* Transplant
* Malignancy
* Connective Tissue Disorders / Autoimmune
* Drugs - Tacrolimus
* Toxins
Diagnoses of TTP
THE PENTAD:
A. LABORATORY:
- Thrombocytopenia
-Platelet count <20-30 x 109/L - Micro-angiopathic haemolytic anaemia (MAHA)
-Schistocytes / red cell fragmentation on the peripheral blood smear (PBS)
-Haemolytic screen: Elevated LDH, low haptoglobin, elevated reticulocyte production index (RPI), elevated unconjugated hyperbilirubinaemia,
negative Coomb’s test
-(Coagulation screen are typically normal)
B. CLINICAL:
- Neurological deficits/abnormalities
- Renal dysfunction/failure
- Fever
C. Confirmation of the ADAMTS13 deficiency
*Deficiency of the ADAMTS13 activity level
* ADAMTS13 antigen levels vary
Management of TTP
- Supportive:
*Avoid Platelet Transfusion
*Aim for optimal haemoglobin (Hb)
*Monitor for seizures, exclude acute coronary syndromes
*Folic acid
*Fluid resuscitation and maintenance
*Find and Treat the cause (e.g. HIV = ART)
*Consider Prednisone 1mg/kg/day (↓ circulating auto-antibodies)
*Anticoagulation/antiplatelet when platelet count > 50 x 109/L - Specific:
*Therapeutic Plasma Exchange (TPE)
*Solvent Detergent (S/D) Fresh Frozen Plasma (FFP) may be used in the interim
Characteristics of inherited qualitative platelet disoders
- Rare, described in few families
- Mild: presents later in life, with haemostatic challenge
- Severe: from early childhood or neonate
- Specialist management: haemophilia centre or
specialised bleeding disorder centre
Name all the characteristics of Glanzmann thrombasthenia as one of the qualitative platelet disoders
- Autosomal Recessive
- Platelet aggregation disoder
- Glycoprotein IIb/IIIa
- Severe mucocutaneous bleeding
- Normal platelet count with normal sized platelets
- No aggregation on addition of ADP, collagen, Adrenaline, Arachidonic acid
- Flow Cytometry: GPIIb(CD41)/IIIa(CD61) deficient
Name all the characteristics of Bernard-Soulier Syndrome, as one of the qualitative platelet disoders
- Autosomal Recessive
- Platelet adhesion disoder
- Glycoprotein Ib/IX/V
- Mild-moderate mucocutaneous bleeding
- Thrombocytopenia (to normal) with large platelets
- Aggregation is absent with the addition of Ristocetin
- Flow Cytometry: GPIb(CD42b) deficient
List 3 qualitative acquired platelet disoders
- Systemic
* Renal disease – Uremia → impaired vessel wall-platelet and platelet-platelet interaction
* Liver disease – abnormal aggregation to ADP - Haematologic
* Myelodysplasia (MDS) – impaired platelet aggregation
* Myeloproliferative neoplasm (MPN) – leucocyte-platelet interaction, storage pool
deficiency, impaired platelet aggregation, decreased glycoprotein expression and
fibrinogen binding after platelet activation
* Paraproteinaemia (Myeloma) – adsorption of abn. proteins onto platelet membranes - Drugs
* Cyclo-oxygenase inhibitors: Salicylates (Aspirin), NSAIDs prevents platelet aggregation
* Platelet Receptor Antagonists:
*Glycoprotein IIb/IIIa inhibitors (abciximab)
*Thienopyridines P2Y12 inhibitors (clopidogrel)
* SSRIs (fluoxetine): diminished serotonin release on platelet activation → decreased
platelet aggregation
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Name the 2 types of bleeding patterns
- Platelet type
-From defect in primary hemostasis
-Characterized by mucosal cutenous bleeding
-Petechiae - Clotting factor type
-From defect in 2nday hemostasis
-Characterized by bleeds into muscles, joints, internal organs
-Ecchymoses
Investigation of Platelet Disorders
- Screening Tests
*Full Blood Count (FBC) and Peripheral Blood Smear (PBS)
*Bleeding Time
* Platelet Function Assay - Diagnostic Tests
*Platelet Aggregation Studies
*Flow Cytometry
*(Gene Sequencing
