W8CL2 - Disorders of Platelets Flashcards
Measurement of Platelets - Siemens Advia 120
Classified by size & refractive index Categories: - platelets - large platelets - (RBC ghosts, RBC fragments, debris) Good differentiation from RBC Micro-aggregates (3-4 platelets) of platelets may be identified/reported as large platelets
Platelet Flags - LRI and URI
LRI - lower region interference - very small structures - debris, microbubbles, bacteria, etc. URI - upper region interference - region of overlap between small RBC and large platelets
Von Willebrand Factor
VWF is a protein that is assembled from identical subunits into linear ‘strings’
When vascular injury occurs, VWF becomes tethered to the exposed area
Conformational change in VWF promotes platelets to adhere, become activated, and then aggregate
Von Willebrand disease (VWD) is an inherited disorder of coagulation characterised by a quantitative or qualitative abnormality of VWF
Von Willebrand Disease is not a disorder of platelets
However, quantitative or qualitative disorders of VWF will compromise platelet function
Von Willebrand Disease
The clinical signs of VWD are very similar clinical signs to platelet disorders Classification of VWD: Type 1 - partial quantitative deficiency of VWF Type 2 - qualitative deficiency of VWF - includes fours sub-types (A, B, M, N) Type 3 - virtually complete deficiency of VWF
Thrombocytosis
Thrombocytosis is typically discovered as an incidental finding in a FBC
Thrombocytosis either:
- is caused by a clonal bone marrow (myeloproliferative) disorder e.g. essential thrombocythaemia (ET)
- or a reactive process (secondary thrombocytosis)
Secondary Thrombocytosis
[Platelet] > 500 x 10^9/L
The most frequent underlying causes:
- tissue damage due to major surgery, infection, cancer, and chronic inflammation
Thrombocytopenia
Decreased concentration of platelets Haemorrhage is typically petechial/purpural Haemorrhage may occur at: - less than 10 x 10^9/L; commonly occurs - 20-30 x 10^9/L; may occur - 100 x 10^9/L; may occur with haemostatic challenge (e.g. surgery) 3 general mechanisms - decreased production - altered distribution - increased destruction
Thrombocytopenia - Decreased Production
Decreased [platelet] in the peripheral blood Decreased numbers of megakaryocytes in the bone marrow Many causes: 1. Marrow damage - aplasia - drugs/toxins - neoplasia 2. Congenital defects - Fanconi anaemia - May-Hegglin anomaly - Wiskott-Aldrich syndrome 3. Ineffective production - B12/Folate deficiency
Thrombocytopenia - Altered Distribution
Platelets available for haemostasis include circulating pool & ‘exchangeable’ pool of platelets in the spleen
Typically comprise ~ 1/3 of total platelets
Conditions => splenomegaly => platelet sequestration
Typically not below 40 x 10^9/L
Thrombocytopenia - Increased Destruction (Immune and Non-Immune Causes)
Non-immune
- disseminated intravascular coagulation (DIC)
- haemolytic-uraemic syndrome (HUS)
- thrombotic thrombocytopenic purpura (TTP)
Immune
- drug induced thrombocytopenia
- heparin induced thrombocytopenia (HIT)
- idiopathic thrombocytopenic purpura (ITP)
- secondary to other disorders (e.g. viral disease, SLE)
Disseminated Intravascular Coagulation (DIC)
Non-immune mechanism
Clotting proteins, inhibitors & platelets are consumed faster than they are synthesized
=> ‘consumptive coagulopathy’
- acquired deficiency of multiple hemostatic components
- fibrinolysis follows fibrin formation
- patient generally bleeds at same time that disseminated clotting is occurring
Many inciting causes
- e.g. sepsis, massive trauma
Thrombotic Thrombocytopenic Purpura (TTP)
Non-immune mechanism
Microangiopathic destruction of platelets
Low grade fever, microangiopathic haemolytic anaemia, schistocytosis
DIC screen otherwise normal
May be congenital; sporadic/idiopathic; or following drug therapy
Increased platelet destruction occurs following platelet ‘activation’
The congenital & sporadic forms of TTP occurs due to ↓ vWF cleaving protein (ADAMTS13)
Assay of ADAMTS13 is used to support diagnosis
Immune-Mediated Thrombocytopenia in Adults
Mechanism: effected through destruction of platelets
Typically: decreased [platelet] in the PB with ‘normal’/increased megakaryocytes in the BM
Many causes:
1. Association with drugs
- e.g. quinidine; act as hapten to incite antibody formation
2. Association with heparin (HIT)
- several forms
- type I; passive binding of heparin; transient, mild
- type II; form antibodies to heparin-platelet factor 4 complex
- => ↑ clearance of platelets
Idiopathic Thrombocytopenic Purpura
Idiopathic thrombocytopenic purpura (ITP) is characterised by decreased platelet production & premature destruction of autoantibody-coated platelets => thrombocytopenia
Thrombocytopenia can persist for months to years
Generally, patients require treatment if:
- they are bleeding
- low platelet counts (<20 × 10^9/L)
- prior to scheduled surgical procedures
ITP can present either alone (primary) or in the setting of other conditions (secondary), such as infections or altered immune states
ITP is associated with a loss of tolerance to platelet antigens => accelerated platelet destruction & impaired platelet production
Post Viral Thrombocytopenia
Most commonly observed in children 1-2 weeks post-viral infection - rubella, rubeola, chickenpox, respiratory viral infections - may also be incited by live vaccines Widespread petechiae, purpura Platelets < 100 x 10^9/L ↑ ‘reticulated’ platelets Bone marrow; normal to ↑ megakaryocytes Diagnosis usually clinical
