Thrombocytopathies

Pathogenetic classification

For better understanding of the pathological process, hereditary platelet function disorders are grouped according to the stages of platelet hemostasis:

1. Adhesion disorders (impaired attachment to the subendothelium). The problem lies in the receptor apparatus or binding proteins. For example, Bernard–Soulier syndrome involves the GPIb-IX-V complex, while von Willebrand disease lacks the von Willebrand factor, which acts as a "bridge".
2. Aggregation disorders (impaired cell clumping). A prominent example is Glanzmann thrombasthenia, which features a defect in the main fibrinogen receptor (the GPIIb-IIIa complex).
3. Degranulation disorders (storage pool deficiency). These occur when there is a shortage of $\alpha$-granules (gray platelet syndrome) or dense $\delta$-granules.
4. Signaling pathway defects and structural anomalies. The largest group, including failures at the level of receptors, G-proteins, arachidonic acid metabolism (blocked thromboxane synthesis), and cytoskeletal defects.

Classification by size and hallmark syndromes

Evaluation of platelet size in a peripheral blood smear is the most accessible basic method of differential diagnosis, especially in combined pathologies.

• Microcytic forms (small platelets). These include Wiskott–Aldrich syndrome (WASP protein mutation). The classic form manifests as a severe triad: bleeding tendency, profound immunodeficiency, and atopic dermatitis (eczema). A milder variant also exists — X-linked thrombocytopenia without eczema.
• Normocytic forms. A typical example is Glanzmann thrombasthenia. The GPIIb-IIIa receptor complex may be quantitatively absent (types 1 and 2) or present but non-functional (type 3). An important diagnostic marker: aggregation with ADP and collagen is absent, but is preserved only upon the addition of ristocetin.
• Macrocytic forms (giant platelets). This category includes Bernard–Soulier syndrome. Unlike von Willebrand disease, the level of the factor itself is normal, but its receptors are defective. Aggregation with ristocetin is completely absent.
• MYH9-related syndromes. Autosomal dominant disorders where macrothrombocytopenia is combined with renal impairment, sensorineural hearing loss, and cataracts. A specific marker is large basophilic inclusions (Dhle bodies) in monocytes and granulocytes.

Diagnostic algorithm

The diagnostic workup for suspected thrombocytopathy should be step-by-step:

1. Blood smear analysis. Manual cell counting and visual assessment of morphology (size, staining) using Romanowsky–Giemsa stain are mandatory. For example, in gray platelet syndrome, cells are large and pale due to the absence of $\alpha$-granules.
2. Evaluation of primary hemostasis. Endothelial capillary fragility tests and bleeding time tests (Duke or Ivy methods) are performed, which are characteristically prolonged in thrombocytopathies.
3. Light transmission aggregometry. The method is based on photometric recording of changes in light transmission of platelet-rich plasma. Inducers (ADP, collagen, epinephrine, ristocetin) are added sequentially to the plasma, and the percentage of aggregation is evaluated.
4. Molecular genetic testing. Search for specific mutations (e.g., in MYH9, WASP genes, or receptor subunits) for final verification.

Principles of treatment

Therapy for thrombocytopathies is symptomatic. Antifibrinolytic agents (tranexamic acid) and angioprotectors (etamsylate) are used. Magnesium preparations, ATP, and vitamins C and P are prescribed in courses for metabolic platelet support.

It is extremely important to avoid physiotherapeutic procedures and medications that inhibit platelet function. This primarily applies to nonsteroidal anti-inflammatory drugs (NSAIDs), the use of which is strictly prohibited in thrombocytopathies.

What else to study on this topic

• Structure of platelet glycoprotein receptor complexes (GPIIb/IIIa and GPIb-IX-V)
• Physiology and biochemistry of platelet granules (alpha and delta pools)
• Interpretation of light transmission aggregometry results
• Differential diagnosis of MYH9-related syndromes and systemic lupus erythematosus
• The role of von Willebrand factor in primary hemostasis

Other topics in "Chapter 10. Diseases of the Blood and Blood-Forming Organs"

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