Thrombocytopenia causes and diagnosis

• Platelet abnormalities cause haemorrhagic disorders; these are generally due to quantitative defects like thrombocytopenia, or qualitative defects known as platelet function disorders.

Causes of Thrombocytopenia

• Failure of platelet production within the body.
• Elevated consumption or destruction of platelets.
• Aberrant distribution of platelets throughout the body.
• Dilution effect, which can lower platelet concentration.

Failure of Platelet Production

• Selective megakaryocyte depression can occur from rare congenital defects, such as May-Hegglin anomaly and Wiskott-Aldrich syndrome.
• Selective depression can also be caused by drugs, chemicals, and certain viral infections like CMV and EPV.
• General bone marrow failure may happen due to cytotoxic drugs, radiotherapy, or conditions like aplastic anaemia, leukaemia, myelodysplastic syndromes, myelofibrosis, or HIV infection.
• Diagnosis involves considering the clinical history, peripheral blood count, blood film analysis, and bone marrow examination.

Increased Consumption/Destruction of Platelets

• Immune-mediated mechanisms : idiopathic thrombocytopenic purpura (ITP), drug-induced reactions, and infections. Post-transfusion purpura is another immune-mediated cause.
• Non-immune mediated mechanisms : disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura (TTP).

Autoimmune (Idiopathic) Thrombocytopenic Purpura (ITP)

• Autoimmune thrombocytopenic purpura (ITP) is divided into chronic and acute forms.
• The acute form is more common in children.
• In 75% of cases, acute idiopathic thrombocytopenic purpura follows vaccination or an infection such as chickenpox or infectious mononucleosis.
• Spontaneous remissions happen frequently, but in 5-10% of cases, the disease becomes chronic, lasting over 6 months.
• Diagnosis involves excluding all other underlying causes, with bone marrow aspiration debated.
• If a patient's platelet count is above 30 x 10^9 /L, treatment is only required if bleeding is severe.
• For counts below 20 ×10^9/L, steroids may be used, especially if there is significant bleeding.

Chronic Idiopathic Thrombocytopenic Purpura

• This is a relatively common disorder.
• The highest incidence is in women aged 15-50.
• The cause of thrombocytopenia is idiopathic but may be linked to systemic lupus erythematosus (SLE), HIV infection, CLL, Hodgkin's disease, or autoimmune haemolytic anaemia.

Pathogenesis

• Platelet autoantibodies are usually IgG.
• The antibody targets antigen sites on the glycoprotein (GP).
• Platelet lifespan goes from 7-10 days to a few hours in ITP.
• Total megakaryocyte mass and platelet turnover are increased to approximately five times normal.

Clinical Features

• Easy bruising is a common symptom.
• Women may experience menorrhagia.
• Mucosal bleeding, like nosebleeds or gum bleeding, occurs in severe cases.

Diagnosis

• Platelet count is typically between 10-50 x 10^9 L.
• Haemoglobin concentration and WBC counts are normal unless there is iron deficiency anaemia.
• A blood film shows reduced numbers of platelets.
• Bone marrow shows normal or increased numbers of megakaryocytes.
• Specific anti-glycoprotein GPIIb or GPIb antibodies can be found on the platelet surface or in the serum.

Treatment

• Aims to maintain a platelet count above the point where spontaneous bruising or bleeding occurs.
• For platelet counts above 50 x 10^9 /L, treatment is generally not required.
• Treatment options include corticosteroids, splenectomy, and immunosuppressive drugs.

Non-Immune Disseminated Intravascular Coagulation

• Thrombocytopenia can result from an increased rate of platelet destruction due to their consumption in disseminated intravascular coagulation (DIC).

Non-Immune Thrombotic Thrombocytopenic Purpura (TTP)

• Thrombotic Thrombocytopenic Purpura can be congenital or acquired.
• It is more common in women than in men.
• There is a deficiency of ADAMTS13 metalloprotease, which breaks down ultra large von Willebrand factor multimers (ULVWF).
• ULVWF is anchored to endothelial cells, allowing platelets to adhere via GPIb receptors.
• Increased platelet aggregation onto ULVWF multimers can form large, occlusive platelet thrombi.
• Consequently, platelet counts are low in circulation.
• Coagulation tests are normal, in contrast to DIC findings.
• ADAMTS13 is absent or severely reduced in plasma.
• Treatment involves plasma exchange using fresh frozen plasma (FFP) or cryosupernatant.

Qualitative Platelet Disorders

• These disorders are divided into two categories: hereditary and acquired.
• Hereditary disorders may cause defects in platelet reactions, affecting haemostatic platelet plug formation.

Bernard-Soulier Syndrome

• In Bernard-Soulier syndrome, platelets are larger than normal.
• Deficiency of GPIb (chromosome 22) is present.
• There is defective binding to von Willebrand factor (VWF).
• Defective adherence to exposed subendothelial connective tissues occurs.
• There is variable thrombocytopenia.
• The disorder is often noticed in childhood.
• Children have frequent bruises, nose bleeds, and bleeding in the mouth and gums.
• Some individuals might experience gastrointestinal bleeding.
• Women may experience heavy menstrual bleeding also known as menorrhagia.
• Laboratory diagnosis will show prolonged bleeding time, low platelet count, platelets that appear larger than normal under a microscope, and platelets that do not clump together in response to ristocetin.

Glanzmann's Disease

• This autosomal recessive disorder leads to primary platelet aggregation failure.
• The failure is due to a membrane GPIIb deficiency (gene on chromosome 17).
• Glanzmann's disease presents in the neonatal period.
• Platelets fail to aggregate in vitro to any agonist except ristocetin, characteristically.
• Laboratory diagnosis shows prolonged bleeding time and platelets that do not clump together (platelet aggregation is absent).

Acquired Platelet Function Disorders

• Platelet function can be affected by common drugs, like aspirin and other drugs containing aspirin, and non-steroidal anti-inflammatory drugs like ibuprofen.
• Other drugs that can affect platelets include some antibiotics, heart drugs, blood thinners, antidepressants, anaesthetics, and antihistamines.
• Platelet function returns to normal after these medications are stopped.

Thrombocytopenia, a quantitative platelet defect, arises from factors like impaired platelet production, increased platelet consumption or destruction, abnormal platelet distribution, or dilution effects. Production failure stems from megakaryocyte depression due to congenital defects or external factors like drugs and viral infections. General bone marrow failure is another cause.