Hymolysis

Question 1

Haptoglobin

methemoglobin

methaemalbumin

hemosiderinuria

Question 2

Causes of hemolytic anemia:

Answer 2

Inherited red cell abnormalities:

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 

Red cell membrane defects: resulting in chronic hemolytic anemia may arise from pathologies of the red cell membrane (hereditary spherocytosis or elliptocytosis).

Abnormal hemoglobin (hemoglobinopathies) Abnormality in protective enzymes which prevent cellular oxidative damage, such as glucose6-phosphate dehydrogenase (G6PD).

Acquired causes: include auto- and allo-antibody-mediated destruction of red blood cells and other

mechanical, toxic and infective causes. Paroxysmal Nocturnal Hemoglobinuria

Question 3

Hereditary spherocytosis:

Answer 3

Autosomal dominant condition, asymptomatic compensated chronic hemolytic state with spherocytes present on the blood film, a reticulocytosis and mild hyperbilirubinaemia

Question 4

Hereditary spherocytosis: stones

Answer 4

Pigment gallstones are present in up to 50% of patients and may cause symptomatic cholecystitis

Question 5

❛ Hereditary spherocytosis ❜

❛ The clinical course may be complicated by crises: ❜
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Answer 5

❛ Hemolytic crisis: occurs when the severity of hemolysis increases; this is rare, and usually associated with infection.

Megaloblastic crisis: follows the development of folate deficiency; this may occur as a first presentation of the disease in pregnancy.

Aplastic crisis: occurs in association with erythrovirus infection( Parvovirus B19 (=Fifth disease

(erythema infectiosum) .Erythrovirus causes a common exanthem in children, but if individuals with chronic hemolysis become infected, the virus directly invades red cell precursors and temporarily switches off red cell production. Patients present with severe anemia and a low reticulocyte count. ❜
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Question 6

Hereditary spherocytosis:

clinical course may be complicated by crises:

Answer 6

Hemolytic crisis: occurs when the severity of hemolysis increases; this is rare, and usually associated with infection.

Megaloblastic crisis: follows the development of folate deficiency; this may occur as a first presentation of the disease in pregnancy.

Aplastic crisis: occurs in association with erythrovirus infection( Parvovirus B19 (=Fifth disease

(erythema infectiosum) .Erythrovirus causes a common exanthem in children, but if individuals with chronic hemolysis become infected, the virus directly invades red cell precursors and temporarily switches off red cell production. Patients present with severe anemia and a low reticulocyte count.

Question 7

Investigations of spherocytosis

Answer 7

The blood film will show spherocytosis , MCHC is increased due to loss of membrane and the consequent spherical shape assumed by the cell.

direct Coombs test is negative excluding immune hemolysis , An osmotic fragility test show lysis in hypotonic saline solutions but is limited by lack of sensitivity and specificity.

More specific flow cytometric tests, detecting binding of eosin-5-maleimide to red cells, are recommended in borderline cases.

Question 8

Management

Answer 8

Folic acid prophylaxis, 5 mg once weekly, should be given for life. Splenectomy after age 7 years indications in moderate to severe hemolysis with complications (anemia and gallstones), Acute, severe hemolytic crises require blood transfusion, but blood must be cross-matched carefully and transfused slowly as hemolytic transfusion reactions may occur.

Question 9

Hereditary Elliptocytosis mode of inheritance is

Answer 9

autosomal dominant. In most cases no symptoms and requires no therapy. For patients with clinically significant hemolytic anemia, splenectomy provides marked improvement.

Question 10

Glucose-6-phosphate dehydrogenase (G6PD) deficiency:

This is usually inherited

Answer 10

x linked inherited ,The deficiency therefore affects males and rare homozygotic females There are over 400 subtypes of G6PD described A+ A-, B+, B-

Question 11

Clinical features of g6pd

Answer 11

Favism, i.e. acute hemolysis after ingestion of the fava bean Acute drug-induced hemolysis (e.g.)

o Analgesics: aspirin,paracetamol

o Antimalarials: primaquine, quinine, chloroquine, pyrimethamine

o Antibiotics: sulphonamides, nitrofurantoin, ciprofloxacin

o Miscellaneous: quinidine, probenecid, vitamin K, dapsone Chronic compensated hemolysis Infection or acute illness Neonatal jaundice: may be a feature of the B - enzyme

Question 12

blood film will show in g6pd

Answer 12

Bite cells (red cells with a ‘bite’ of membrane missing) Blister cells (red cells with surface blistering of the membrane) Irregularly shaped small cells  

Polychromasia reflecting the reticulocytosis Denatured hemoglobin visible as Heinz bodies within the red cell cytoplasm, if stained with a supravital stain such as methyl violet.

Question 13

spherocytes are present in the blood. In Autoimmune hemolytic anemia

Answer 13

Antibody-coated red cells lose membrane to macrophages in the spleen

Question 14

Warm antibodies

Cold antibodies:

Answer 14

Warm antibodies: bind best at 37 °C and account for 80% of cases. The majority are IgG Cold antibodies: bind best at 4 °C but can bind up to 37 °C in some cases. They are usually IgM and bind complement. They account for the other 20% of cases.

Question 15

Warm autoimmune hemolysis

secondary to a wide variety of other condition

Answer 15

Lymphoid neoplasms: lymphoma, chronic lymphocytic leukemia, myeloma

-Solid tumors: lung, colon, kidney, ovary, thymoma

-Connective tissue disease: SLE, rheumatoid arthritis -

-Drugs: methyldopa, mefenamic acid, penicillin, quinidine

-Miscellaneous: ulcerative colitis, HIV

Question 16

Investigations Warm autoimmune hemolysis :

Answer 16

blood film evidence of hemolysis and spherocytosis. The diagnosis is confirmed by the Direct Coombs( antiglobulin) test The antiglobulin test is used to determine autoimmune hemolytic anemia, a disease in whicht the RBC attacked and destroyed by antibodies produced by their own bodies.

There are two types of antiglobulin tests: direct and indirect

Question 17

Management

Warm autoimmune hemolysis :

Answer 17

If the hemolysis is secondary to an underlying cause, this must be treated and any offending drugs stopped. Prednisolone 1 mg/kg orally. A response is seen in 70-80% of cases but may take up to 3 weeks; a rise in hemoglobin will be matched by a fall in bilirubin, LDH and reticulocyte levels. Once the hemoglobin has normalized and the reticulocytosis resolved, the corticosteroid dose can be reduced slowly over about 10 weeks. Corticosteroids work by decreasing macrophage destruction of antibody-coated red cells and reducing antibody production.

Blood Transfusion may be required for life-threatening problems, such as the development of heart failure or rapid decrease in Hb.

Splenectomy should be considered If the hemolysis not respond to corticosteroids or can only be stabilised by large doses.

immunosuppressive therapy with azathioprine or cyclophosphamide may be considered The anti-CD20 (B cell) monoclonal antibody, rituximab, has shown some success in difficult cases.

Question 18

Chronic cold agglutinin disease:

Answer 18

This affects elderly patients and may be associated with an underlying low-grade B cell lymphoma. It causes a low-grade intravascular hemolysis with cold, painful and often blue fingers, toes, ears or nose (so-called acrocyanosis).

The blood film shows red cell agglutination and the MCV may be spuriously raised because the automated analyzers count aggregates as single cells.

The monoclonal IgM usually has specificity against the red cell antigen and is present in a very high titre

Question 19

Cold agglutinin disease: Treatment

Answer 19

Treat underline disease and if idiopathic, then patients must keep extremities warm, especially in winter. Some patients respond to corticosteroid therapy and blood transfusion may be considered, but the crossmatch sample must be placed in a transport flask at a temperature of 37 °C and blood administered via a blood-warmer.

Other causes of cold agglutination can occur in association with Mycoplasma pneumoniae or with infectious mononucleosis

Question 20

Non-immune hemolytic anemia:

Answer 20

Non-immune hemolytic anemia:

Question 21

Paroxysmal Nocturnal Hemoglobinuria (PNH)

It is a rare, acquired, potentially life-threatening disease of the blood characterized by……………. induced intravascular hemolytic anemia

Answer 21

complement

Question 22

Paroxysmal Nocturnal Hemoglobinuria (PNH) associated with ….

Answer 22

increased risk of venous thrombosis as pul. embolism and unusual sites such as the liver or abdomen. CNS. PNH is also associated with hypoplastic bone marrow failure, aplastic anemia and myelodysplastic syndrome

Question 23

PNH is the only hemolytic anemia caused by an

Answer 23

acquired (rather than inherited) intrinsic defect in the cell membrane (deficiency of glycophosphatidylinositol leading to absence of protective proteins on the membrane).

Question 24

Investigation PNH

Hams test

Answer 24

Intravascular hemolysis: low Hb, high LDH, high retic count, high bilirubin( indirect),low haptoglobin,-ve coombs test, microcytic RBC Hams test The test involves placing red blood cells in mild acid; a positive result (increased RBC fragility) Confirmation by flow cytometry for CD55 and CD59 on WBC and RBC.

Question 25

Management PNH

Answer 25

supportive with Folic acid supplements ,blood transfusion and treatment of thrombosis. Recently the anti-complement C5 monoclonal antibody ecluzimab(Soliris) was shown to be effective in reducing haemolysis.and reducing the need for blood transfusions, improving quality of life, and reducing the risk of thrombosis.

is the only curative therapy,Allogeneic bone marrow transplantation