Makindo Medical Notes

Related Subjects: |Microangiopathic Haemolytic anaemia |Haemolytic anaemia |Immune(Idiopathic) Thrombocytopenic Purpura (ITP) |Thrombotic Thrombocytopenic purpura (TTP) |Haemolytic Uraemic syndrome (HUS) |Thrombocytopenia |Disseminated Intravascular Coagulation (DIC)

Thrombotic microangiopathies (TMA) are a group of related disorders characterized by thrombosis of the microvasculature and associated organ dysfunction.

About Microangiopathic Haemolytic Anaemia (MAHA)

• A form of haemolytic anaemia caused by red cell destruction within the microvasculature.
• RBCs have a shortened lifespan (often less than 100 days) due to mechanical damage.
• Schistocytes (fragmented RBCs) appear in blood films and are often described as "helmet cells," showing small, irregular triangular shapes.

Types of MAHA

• Thrombotic Thrombocytopenic Purpura (TTP): Characterized by anaemia, low ADAMTS13 levels, low platelets, erythrocyte polychromasia, anisocytosis, and prominent schistocytes.
• Haemolytic-Uraemic Syndrome (HUS): Often associated with renal failure; frequently follows infection with Escherichia coli producing shiga toxin.
• Disseminated Intravascular Coagulation (DIC): A secondary condition involving widespread clotting that leads to RBC fragmentation.
• Heparin-Induced Thrombocytopenia (HIT): Triggered by heparin exposure (typically 5-14 days post-exposure), associated with large-vessel thrombosis and anti-platelet factor 4 antibodies.
• Paroxysmal Nocturnal Haemoglobinuria (PNH): Rare condition involving complement-mediated RBC destruction, often presenting with MAHA and thrombocytopenia.

Aetiology

• Fibrin clots form in small vessels, leading to shearing forces on RBCs as they pass through, resulting in cell fragmentation and destruction.

Clinical Presentation

• Symptoms vary depending on the specific type and clinical context of MAHA.
• Neurological symptoms: Seen with TTP, including confusion, headaches, or seizures.
• Renal failure: Often present in cases of HUS, with features like haematuria and oliguria.

Differential Diagnosis

• Disseminated Intravascular Coagulation (DIC).
• Haemolytic Uraemic Syndrome (HUS): Endothelial damage due to E. coli shiga toxin or complement dysregulation.
• Malarial infection with visible parasites in RBCs.
• Thrombotic Thrombocytopenic Purpura (TTP).
• Malignant hypertension.
• Severe pre-eclampsia, especially in pregnancy.
• Mechanical heart valves causing shear stress on RBCs.
• Sickle cell anaemia presenting with haemolysis and vaso-occlusion.
• Systemic sclerosis (scleroderma) with renal crisis leading to microangiopathic features.

Investigations

• Haemoglobin (Hb): Low levels indicate anaemia; low platelet counts may also be present.
• Reticulocyte Count: Increased reticulocytes reflect compensatory marrow response.
• Unconjugated Bilirubin: Elevated due to RBC breakdown.
• Lactate Dehydrogenase (LDH): Raised levels indicate cell turnover and haemolysis.
• Haptoglobin: Low levels suggest intravascular haemolysis.
• Direct Antiglobulin Test (DAT): Negative in MAHA, differentiating it from autoimmune haemolytic anaemia.
• Blood Film: Schistocytes, helmet cells, and polychromasia are characteristic of MAHA.
• Urinary Haemosiderin: Positive in chronic intravascular haemolysis, such as in PNH or mechanical heart valve haemolysis.
• Clotting Tests: Normal APTT and PT, unless complicated by DIC.
• Flow Cytometry: Tests for CD55 and CD59 antigens are used to confirm PNH.

Management

• Treat the underlying cause: Management depends on the specific type of MAHA, such as plasma exchange for TTP or supportive care for DIC.
• Plasma Exchange: Primary treatment for TTP, helping to remove antibodies against ADAMTS13.
• Plasma Infusion: May be necessary to replace deficient ADAMTS13 in some cases.
• Supportive Care: Includes transfusions if severe anaemia or thrombocytopenia, as well as renal support in cases with renal involvement.

References

• Diagnostic Approach to Microangiopathic Haemolytic Disorders