Microangiopathic Autoimmune Hemolytic anemia - Clinicals, Diagnosis, and Management

Hematology

Clinicals - History

Fact Explanation
Introduction Microangiopathic Autoimmune Hemolytic anemia is a thrombotic microangiopathy, that occurred due to the endothelial injury of the vessels followed by the activation of clotting system inside the microvasculature forming microthrombi. When the red blood cells are passing through these micrthrombi, they will undergo destruction causing haemolyss. MAHA is associated with various disease conditions including idiopathic thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), and vasculitis. This may be familial, idiopathic or acquired secondary to toxins, pregnancy, infections (e.g., HIV, certain Shigella and E. coli) and drugs. Patients with some solid organ cancers may also present MAHA. There can be platelet aggregation and thrombus formation, platelet consumption, impaired microvascular blood flow, and mechanical destruction of erythrocytes. Introduction
Microangiopathic Autoimmune Hemolytic anemia is a thrombotic microangiopathy, that occurred due to the endothelial injury of the vessels followed by the activation of clotting system inside the microvasculature forming microthrombi. When the red blood cells are passing through these micrthrombi, they will undergo destruction causing haemolyss. MAHA is associated with various disease conditions including idiopathic thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), and vasculitis. This may be familial, idiopathic or acquired secondary to toxins, pregnancy, infections (e.g., HIV, certain Shigella and E. coli) and drugs. Patients with some solid organ cancers may also present MAHA. There can be platelet aggregation and thrombus formation, platelet consumption, impaired microvascular blood flow, and mechanical destruction of erythrocytes.
Lethargy, Malaise, fatigue Anaemia causes reduced blood oxygenation, leading to reduced supply of oxygen to the energy production. Therefore they feel lack of energy. Lethargy, Malaise, fatigue
Anaemia causes reduced blood oxygenation, leading to reduced supply of oxygen to the energy production. Therefore they feel lack of energy.
Dark urine Suggestive of intravascular haemolysis leading to haemoglobinuria. Dark urine
Suggestive of intravascular haemolysis leading to haemoglobinuria.
Right hypochondrial pain May be present due to associated gallstones due to high level of bilirubin in the blood. Right hypochondrial pain
May be present due to associated gallstones due to high level of bilirubin in the blood.
Features of thrombotic thrombocytopenic purpura: fever, visual disturbances, mental state changes, urinary problems Thrombotic thrombocytopenic purpura (TTP) is a disease where MAHA is associated with the other features due to the vascular occlusions of the microcirculation. Features of thrombotic thrombocytopenic purpura: fever, visual disturbances, mental state changes, urinary problems
Thrombotic thrombocytopenic purpura (TTP) is a disease where MAHA is associated with the other features due to the vascular occlusions of the microcirculation.
Features of Haemolytic uraemic syndrome: diarrhoea, abdominal pain, seizures etc Shiga toxin–producing Escherichia coli are thecause for the diarrhea-associated HUS. It causes haemolysis with mocroangiopathic changes. Features of Haemolytic uraemic syndrome: diarrhoea, abdominal pain, seizures etc
Shiga toxin–producing Escherichia coli are thecause for the diarrhea-associated HUS. It causes haemolysis with mocroangiopathic changes.
Factors in favour of of Disseminated intravascular Coagulation Disseminated intravascular coagulation (DIC) occurs due to sequential activation of the coagulation and fibrinolytic system. Trauma and sepsis are the most common precipitating factors. Factors in favour of of Disseminated intravascular Coagulation
Disseminated intravascular coagulation (DIC) occurs due to sequential activation of the coagulation and fibrinolytic system. Trauma and sepsis are the most common precipitating factors.
History of malignancy Microangiopathic hemolytic anemia (MAHA) occurs occasionally as a paraneoplastic syndrome in association with some solid tumors, such as gastric, breast, and lung cancers. MAHA occurs late in the course of disease, in malignant infiltration of bone marrow, or as a side-effect of chemotherapeutic agents. History of malignancy
Microangiopathic hemolytic anemia (MAHA) occurs occasionally as a paraneoplastic syndrome in association with some solid tumors, such as gastric, breast, and lung cancers. MAHA occurs late in the course of disease, in malignant infiltration of bone marrow, or as a side-effect of chemotherapeutic agents.
Bone pain and respiratory symptoms These symptoms are observed in patients with cancer associated MAHA. Bone pain and respiratory symptoms
These symptoms are observed in patients with cancer associated MAHA.
Pregnancy HELLP syndrome may be a cause of MAHA in pregnant mothers. Severe preeclampsis is associated with HEELP syndrome with haemolysis, elevated and low platelets. Pregnancy
HELLP syndrome may be a cause of MAHA in pregnant mothers. Severe preeclampsis is associated with HEELP syndrome with haemolysis, elevated and low platelets.
History of infections HIV is a known association with the MAHA. History of infections
HIV is a known association with the MAHA.
History of drug use Common drugs causing MAHA includes quinine, cyclosporine, ticlopidine, clopidogrel. History of drug use
Common drugs causing MAHA includes quinine, cyclosporine, ticlopidine, clopidogrel.

Clinicals - Examination

Fact Explanation
Pallor Haemoglobin level reduces during an attack, patient develops anaemia due to red cell destruction. Pallor
Haemoglobin level reduces during an attack, patient develops anaemia due to red cell destruction.
Icterus Haemolysis of red blood cells releases bilirubin into the blood causing elevation of unconjugated bilirubin. This accumulated bilirubin causes yellowish discolouration of eyes and mucous membranes. Icterus
Haemolysis of red blood cells releases bilirubin into the blood causing elevation of unconjugated bilirubin. This accumulated bilirubin causes yellowish discolouration of eyes and mucous membranes.
Wasting Solid organ malignancies are known to be associated with the MAHA as a paraneoplastic syndrome. Wasting
Solid organ malignancies are known to be associated with the MAHA as a paraneoplastic syndrome.
Right hypochondrial tendreness Associated with gallstones due to high level of bilirubin in the blood. Right hypochondrial tendreness
Associated with gallstones due to high level of bilirubin in the blood.
Dyspnea It can be either as a result of anemia Respiratory distress is seen in associated lung carcinoma, as MAHA occurs as a paraneoplstic syndrome in such malignancies. Dyspnea
It can be either as a result of anemia Respiratory distress is seen in associated lung carcinoma, as MAHA occurs as a paraneoplstic syndrome in such malignancies.
Breast lump, abdominal lump, features of lung mass (reduced chest expansion, dull percussion note,increased vocal fremitus, reduced breath sounds) Microangiopathic hemolytic anemia (MAHA) occurs occasionally as a paraneoplastic syndrome in association with some solid tumors, such as gastric, breast, and lung cancers. Breast lump, abdominal lump, features of lung mass (reduced chest expansion, dull percussion note,increased vocal fremitus, reduced breath sounds)
Microangiopathic hemolytic anemia (MAHA) occurs occasionally as a paraneoplastic syndrome in association with some solid tumors, such as gastric, breast, and lung cancers.
Focal neurological signs Brain parenchymal ischemia or hemorrhages may occur due to the thrombotic occlusion of either carotids or vertebral arteries. Focal neurological signs
Brain parenchymal ischemia or hemorrhages may occur due to the thrombotic occlusion of either carotids or vertebral arteries.
Fundal examination There will be haemorrhages seen on funduscopy. Fundal examination
There will be haemorrhages seen on funduscopy.

Investigations - Diagnosis

Fact Explanation
Full blood count With low level of Hemoglobin levels due to anemia, reticulocytosis will be evident as a result of hemolysis. . Blood film may show thrombocytopenia in cancer associated MAHA , disseminated intravascular coagulation and many other diseases associated with MAHA. Platelet count may also be reduced in HELLP syndrome. Full blood count
With low level of Hemoglobin levels due to anemia, reticulocytosis will be evident as a result of hemolysis. . Blood film may show thrombocytopenia in cancer associated MAHA , disseminated intravascular coagulation and many other diseases associated with MAHA. Platelet count may also be reduced in HELLP syndrome.
Blood picture This help to distinguish the other forms of anemia Schistocytes are seen on the blood film due to RBC fragmentation. Polychromasia, nucleated red blood cells are also seen on the blood smear. Leucoberythrobastic picture will be seen particularly in malignancy associated MAHA. Blood picture
This help to distinguish the other forms of anemia Schistocytes are seen on the blood film due to RBC fragmentation. Polychromasia, nucleated red blood cells are also seen on the blood smear. Leucoberythrobastic picture will be seen particularly in malignancy associated MAHA.
Haptoglobin level Haptoglobin is involved with binding free Hemoglobin in the blood. Decreased haptoglobin levels are seen in association with intravascular haemolysis. Haptoglobin level
Haptoglobin is involved with binding free Hemoglobin in the blood. Decreased haptoglobin levels are seen in association with intravascular haemolysis.
Direct Coombs' test Negative direct Coombs' test is helpful in excludin autoimmune conditions. Direct Coombs' test
Negative direct Coombs' test is helpful in excludin autoimmune conditions.
Serum levels of total bilirubin Elevated serum levels of total bilirubin is seen due to haemolysis. Serum levels of total bilirubin
Elevated serum levels of total bilirubin is seen due to haemolysis.
Lactate dehydrogenase (LDH) LDH levels are increased due to increased cell breakdown. Lactate dehydrogenase (LDH)
LDH levels are increased due to increased cell breakdown.
Prothrombin time Prolonged prothrombin time is seen in disseminated intravascular coagulation. Prothrombin time
Prolonged prothrombin time is seen in disseminated intravascular coagulation.

Investigations - Management

Fact Explanation
Renal function tests(Serum creatinine, serum electroytes and blood urea) Diarrhea-associated hemolytic uremic syndrome (HUS) causes acute renal failure particularly in children who are younger than 5 years. Renal function tests(Serum creatinine, serum electroytes and blood urea)
Diarrhea-associated hemolytic uremic syndrome (HUS) causes acute renal failure particularly in children who are younger than 5 years.
Urinalysis Urinalysis may be needed in the cases where they present with dark urine to see any red blood cells present in the urine. Urinalysis
Urinalysis may be needed in the cases where they present with dark urine to see any red blood cells present in the urine.
Stool examination/culture Stool of the diarrohoea associated MAHA patients should be cultured for E. coli. Stool examination/culture
Stool of the diarrohoea associated MAHA patients should be cultured for E. coli.
Endoscopy of the upper and lower gastrointestinal tract, abdominal ultrasonograph, thoracic, abdominal, and pelvic computed tomography Solid organ malignancies such as lung, breast and stomach are occasionally a cause for MAHA. Therefore these investigations are done in order to rule out the possibility of solid tumor origin. Endoscopy of the upper and lower gastrointestinal tract, abdominal ultrasonograph, thoracic, abdominal, and pelvic computed tomography
Solid organ malignancies such as lung, breast and stomach are occasionally a cause for MAHA. Therefore these investigations are done in order to rule out the possibility of solid tumor origin.
Bone marrow examination Signet ring cell carcinoma is a malignancy associated with MAHA. Bone marrow metastases of signet ring cell carcinoma with extensive bone marrow necrosis will be seen in such patients. Bone marrow examination
Signet ring cell carcinoma is a malignancy associated with MAHA. Bone marrow metastases of signet ring cell carcinoma with extensive bone marrow necrosis will be seen in such patients.
D-dimer, fibrinogen and fibrin degradation products (FDP) Important to exclude the disseminated intravascular coagulation DIC) as they will have elevated D dimer levels and reduced fibrinogen. FDP will be elevated due to the fibrin degradation in DIC. D-dimer, fibrinogen and fibrin degradation products (FDP)
Important to exclude the disseminated intravascular coagulation DIC) as they will have elevated D dimer levels and reduced fibrinogen. FDP will be elevated due to the fibrin degradation in DIC.
Cold agglutinin assay /Serum IgG and IgM immunoglobulins To rule out the warm and cold types of autoimmune haemolytic anaemia. Cold agglutinin assay /Serum IgG and IgM immunoglobulins
To rule out the warm and cold types of autoimmune haemolytic anaemia.

Management - Supportive

Fact Explanation
Patient education Patient should be educated about the nature of the disease, particularly about the underlying disease condition such as thrombotic thrombocytopenic purpura, dissemnated intravascular coagulation and its complications and treatment options. Patient education
Patient should be educated about the nature of the disease, particularly about the underlying disease condition such as thrombotic thrombocytopenic purpura, dissemnated intravascular coagulation and its complications and treatment options.
Supportive treatment Red cell transfusion may be needed in some occasions with severe anemia. Fresh frozen plasma may be required in thrombotic thrombocytopenic purpura to increase the thrombocytes. Supportive treatment
Red cell transfusion may be needed in some occasions with severe anemia. Fresh frozen plasma may be required in thrombotic thrombocytopenic purpura to increase the thrombocytes.
Monitoring for complications of the treatment With the long term treatment of microangiopathic haemolytic anaemia, especially with prednisolone they can develop complications due to the treatment such as hypertension, glaucoma, severe osteoporosis, and osteoarthritis. Monitoring for complications of the treatment
With the long term treatment of microangiopathic haemolytic anaemia, especially with prednisolone they can develop complications due to the treatment such as hypertension, glaucoma, severe osteoporosis, and osteoarthritis.

Management - Specific

Fact Explanation
Management options Management will be depend on the underlying disease condition of the patient. Drugs causing MAHA such as quinine, cyclosporine, ticlopidine, clopidogrel may need to be stopped where appropriate. Severe preeclampsia associated HEELP syndrome with haemolysis, elevated and low platelets may require delivery of the fetus. Management options
Management will be depend on the underlying disease condition of the patient. Drugs causing MAHA such as quinine, cyclosporine, ticlopidine, clopidogrel may need to be stopped where appropriate. Severe preeclampsia associated HEELP syndrome with haemolysis, elevated and low platelets may require delivery of the fetus.
Management of Thrombotic thrombocytopenic purpura (TTP) Splenectomy is considered as a method of initial management of all patients with TTP. Other management options includes high dose corticosteroids and antiplatelet drugs. Plasma exchange and plasmapharesis to replace the plasma is also an effective treatment for TTP. Management of Thrombotic thrombocytopenic purpura (TTP)
Splenectomy is considered as a method of initial management of all patients with TTP. Other management options includes high dose corticosteroids and antiplatelet drugs. Plasma exchange and plasmapharesis to replace the plasma is also an effective treatment for TTP.
Management of Haemolytic uraemic syndrome Due to the low plasma vitamin E concentrations in patients with haemolytic uraemic syndrome, treatment with the antioxidant vitamin E is gaining popular for the treatment of HUS. Management of Haemolytic uraemic syndrome
Due to the low plasma vitamin E concentrations in patients with haemolytic uraemic syndrome, treatment with the antioxidant vitamin E is gaining popular for the treatment of HUS.
Management of disseminated intravascular coagulation Management of DIC is targeted to treat the underlying pathogenesis. Infections, trauma, liver disease are the common underlying causes of DIC. Infections need appropriate treatment with antibiotics. Plasma and platelet transfusion has to be use cautiously toprevent stimulation of the coagulation system. Available options for the treatment of DIC include plasma and platelet transfusion, anticoagulant administration, and coagulation inhibitor administration. Management of disseminated intravascular coagulation
Management of DIC is targeted to treat the underlying pathogenesis. Infections, trauma, liver disease are the common underlying causes of DIC. Infections need appropriate treatment with antibiotics. Plasma and platelet transfusion has to be use cautiously toprevent stimulation of the coagulation system. Available options for the treatment of DIC include plasma and platelet transfusion, anticoagulant administration, and coagulation inhibitor administration.

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