Platelet Disorders Notes

Thrombopoietin:
- Regulator of platelet production.
- Produced by the liver and kidneys.
- Levels are increased in thrombocytopenia and reduced in thrombocytosis.
- It increases the number and rate of maturation of the megakaryocytes.

Initial attachment of platelets onto vascular subendothelium is a critical step for hemostasis.
Several factors participate in platelet-subendothelium interactions:
- Subendothelial and plasma adhesive proteins
- Their receptors on the platelet membrane
- Rheological factors
Alteration of any of these factors may imply disorders of physiologic hemostasis, leading to thrombosis or bleeding episodes.
Laminin, von Willebrand factor, fibronectin, and different types of collagen are the main components of subendothelial structures.
The binding of von Willebrand factor to subendothelium and to platelet glycoprotein Ib is of critical importance for platelet attachment to subendothelial components.
Subsequent platelet spreading and aggregate formation is mediated by platelet glycoprotein IIb-IIIa.
The contribution of platelets to hemostasis does not depend exclusively on adhesive and cohesive functions mediated by membrane receptors.
Activated platelets offer a phospholipid surface of critical importance for the activation of coagulation mechanisms.

Blanching suggests an intravascular cause (like erythema from a rash). Non-blanching supports purpura.
Palpable purpura supports an inflammatory cause such as vasculitis or a systemic infection.

Platelet disorders are the most common cause of bleeding.
The disorder could be:
- Number (Thrombocytopenia)
- Number (Thrombocytosis)
- Defective function.

Distribution:
- Pseudothrombocytopenia (Platelet clumps)
- Splenomegaly
- Dilutional (Massive transfusion)

History:
- Is the patient bleeding?
- Are there symptoms of a secondary illness? (neoplasm, infection, autoimmune disease)
- Is there a history of medications, alcohol use, or recent transfusion?
- Are there risk factors for HIV infection?
- Is there a family history of thrombocytopenia?
- Do the sites of bleeding suggest a platelet defect?
Assess the number and function of platelets
- CBC with peripheral smear
- Platelet function study (PFA and platelet aggregation studies)
- vWD screen

Immune-mediated acquired disease of adults and children.
Characterized by:
- A low platelet count (<100 \times 10^9/L, transient or persistent).
- An increased risk of bleeding due to impaired clotting mechanism.
- Currently, no definitive diagnostic criteria exist for primary ITP.
- Considered a diagnosis of exclusion.
Primary ITP is characterized by isolated thrombocytopenia (peripheral blood platelet count <100 \times 10^9/L) in the absence of other causes or disorders that may be associated with thrombocytopenia.
Secondary ITP occurs in association with other conditions, such as systemic lupus erythematosus, immunodeficiency states (e.g., immunoglobulin A deficiency), lymphoproliferative disorders (e.g., chronic lymphocytic leukemia, large granular lymphocytic leukemia, and lymphoma); infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV), and can be induced by certain medications such as heparin and quinidine.

In order to exclude other causes of thrombocytopenia, recent updates recommended that basic evaluation should consist of:
- Patient history - necessary to rule out other causes of thrombocytopenia.
- Physical examination - normal except for signs of thrombocytopenia; no adenopathy or splenomegaly.
- Complete blood count showing isolated thrombocytopenia with large platelets.
- Clinical or laboratory evidence for other causes of thrombocytopenia.

(A) T cells are activated upon recognition of platelet-specific antigens on the APCs and therefore induce antigen-specific expansion of B cells.
The B cells, in turn, produce autoantibodies with specificity for glycoproteins expressed on platelets and megakaryocytes.
(B) Circulating platelets bound by autoantibody are removed by Fc receptors predominantly by splenic macrophages.
(C) Autoantibodies also reduce the capacity of megakaryocytes to produce platelets.

Skin purpura, superficial bruising, epistaxis, menorrhagia.
Mucosal hemorrhage is seen in severe cases, and intra-cranial hemorrhage is rare.

Severe inflammation leads to widespread activation of coagulation and formation of microthrombi.
Endothelial damage.
Microthrombi in the circulation.
Generalized platelet aggregation leads to decreased platelets.
Fibrinolysis leads to increased FDPs (Fibrin Degradation Products)

A defect in platelet function is suspected if there is prolonged bleeding time with or without skin or mucosal hemorrhage in the presence of a normal platelet count.

Table 26.2: Main clinical and laboratory findings in hemophilia A, factor IX deficiency (hemophilia B, Christmas disease), and von Willebrand disease.
Table 26.3: Classification of von Willebrand disease.