Hemolytic anemia resident survival guide

Hemolytic anemia Resident Survival Guide
Overview
Causes
FIRE
Diagnosis
Treatment
Do's
Don'ts

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sanjana Nethagani, M.B.B.S.[2]

Synonyms and keywords:: RBC destruction, Hemolysis

Overview

Anemia is defined as a decrease in red blood cell count in the body. Hemolytic anemia results from a premature destruction of RBCs. Hemolysis can be due to either extravascular or intravascular destruction of cells. It is caused by a wide variety of reasons, which include inherited diseases like thalassemia, sickle cell disease etc, infections, autoimmune conditions, bone marrow dysfunction, blood transfusions and certain drugs can also result in hemolytic anemia. The most common presenting symptoms are: fatigue, palpitations, dyspnea, tachycardia and icterus in severe cases. Diagnosis usually requires a battery of tests including, but not limited to a peripheral smear, CBC, serum LDH, bone marrow studies, etc. Treatment is directed by the specific cause and can involve bone marrow transplant, splenectomy, transfusions etc.

Causes

Life threatening causes

• ABO incompatibility
• Disseminated intravascular coagulation
• Thrombotic thrombocytopenic purpura
• Hemolytic uremic syndrome
• Pre-eclampsia and malignant hypertension

Other causes

• Membrane cytoskeletal defects like hereditary spherocytosis and hereditary elliptocytosis
• Glucose 6 phosphate dehydrogenase deficiency
• Pyruvate kinase deficiency
• Sickle cell disease
• Thalassemia
• Cold agglutinin disease
• Drug induced hemolytic anemia
• Systemic lupus erythematosus
• Prosthetic heart valves
• Infectious causes such as malaria, hepatitis, CMV infection etc.

For a complete list of hemolytic anemia causes click here

Diagnosis

The approach to diagnosis of hemolytic anemia is based on a step-wise testing strategy. Below is an algorithm summarizing the identification and laboratory diagnosis of hemolytic anemia.

Characterize the symptoms: ❑ Weakness ❑ Shortness of breath ❑ Jaundice ❑ Lethargy ❑ Chest pain and reduced exercise tolerance ❑ Pica

Examine the patient: ❑ Tachypnea ❑ Cold and clammy skin ❑ Hypotension ❑ HEENT signs: Conjunctival pallor Jaundice ❑ Cardiovascular exam: Tachycardia Systolic murmur ❑ Abdominal exam: Enlarged spleen RUQ pain may indicate bilirubin gallstones ❑ Skin exam: Pallor of nail beds, palmar creases Bronze skin colour in case of repeated transfusions Leg ulcers ❑ Fever and neurological signs are seen in TTP ❑ Hemoglobinuria in some cases

Initial workup for hemolysis: ❑ Indirect bilirubin ❑ serum haptoglobin ❑ Lactate dehydrogenase level ❑ Reticulocyte count ❑ Urinalysis

Peripheral blood smear

No laboratory evidence of hemolysis

Consider differential diagnosis ❑ Iron deficiency anemia ❑ Anemia of chronic disease ❑ Vitamin B12 deficiency ❑ Folate deficiency

Degmacytes

Normal cell morphology

Spherocytes

Elliptocytes

Shistocytes

Sickle shaped cells

Hypochromic, microcytic cells

G6PD deficiency

❑ Family history ❑ Drug history ❑ Recent infections

Coomb's test

Hereditary elliptocytosis

Sickle cell disease

H/o exercise, exertion, trauma or surgery?

Beta thalassemia

Negative

Positive

Yes

No

CD55/59

❑ Drug induced hemolytic anemia ❑ Autoimmune disease

❑Exercise induced hemolysis ❑Prosthetic heart valve ❑Severe aortic stenosis

Microangiopathic hemolytic anemia

Positive

Negative

Pre-eclampsia and eclampsia

Recent diarrhea

Decreased ADAMTS13 activity

Paroxysmal nocturnal hemoglobinuria

Hereditary spherocytosis

HELLP syndrome

Hemolytic uremic syndrome

Thrombotic thrombocytopenic purpura

Treatment

• The treatment of hemolytic anemia depends on the cause of anemia.
• Treatment plan is summarized in the algorithm below based on the 2017 guidelines published by the British Society of Hematology and and the 2020 recommendations by the First International Consensus Group.

History Fatigue Dyspnea Lightheadedness Physical examination Pallor Icterus Cold, clammy skin

Initial investigations Complete blood count Peripheral smear Reticulocyte count Complete urine examination Unconjugated bilirubin Lactate dehydrogenase

Confirm hemolysis Low hemoglobin Elevated lactate dehydrogenase Low haptoglobin High unconjugated bilirubin Reticulocytosis Hemoglobinuria

Peripheral blood smear findings

Shistocytes

Spherocytes

Bite cells

Microangiopathic hemolytic anemia

Direct antibody test

Oxidative stress like G6PD deficiency Consumption of certain foods like fava beans Oxidative drugs such as quinidine, sulfa drugs etc

Further investigations PT/PTT Renal function tests Blood pressure Liver function tests ADAMTS13 level Positive Shiga toxin/EHEC test

Treatment of acute attacks Blood transfusion Hemodialysis Long term measures Avoidance of trigger foods and drugs Splenectomy- spleen is the site of destruction of RBCs Avoid aspirin as it reduces the lifecycle of RBCs Vaccination against common trigger infections such as Hepatitis A& B

Negative Hereditary spherocytosis

Positive Autoantibodies Alloimmunization Drug-induced Treatment of drug induced hemolytic anemia includes removal of offending agent

Treatment for hereditary spherocytosis Currently there is no cure for hereditary spherocytosis Acute attacks of hemolytic anemia are treated with blood transfusions Splenectomy is indicated in severe cases Post-splenectomy, patients are vaccinated against influenza, capsulated bacteria such as S. pneumonia and meningococcus Cholecystectomy is indicated in patients with pigment gallstones

Alloimmunisation treatment Causes: ABO incompatible or Rh incompatible transfusion Stop transfusion immediately Fluid replacement Monitor vital signs Pressor support Hemodialysis If DIC occurs then treatment with fresh frozen plasma, platelet transfusion or cryoprecipitate

Warm type AIHA First-line treatment: Corticosteroids If anemia does not improve with corticosteroids, other immunosuppressants may be considered Second-line: Rituximab, cyclophosphamide, azathioprine, cyclosporine Splenectomy in recurrent disease

Cold type AIHA Avoid cold exposure Rituximab in severe or recurrent disease Treat underlying infection

Thrombotic thrombocytopenic purpura Transfusion is contraindicated Plasmapheresis is treatment of choice Fresh frozen plasma can be given if plasmapheresis is not available Corticosteroids are given concomitantly Rituximab is emerging as a therapy when plasma exchange and corticosteroids fail Refractory TTP is treated with immunosuppressive agents such as cyclophosphamide and vincristine Caplacizumab is another treatment option but it is associated with excess bleeding Hemolytic uremic syndrome Treatment of HUS mainly focus on supportive care Steroids Hemodialysis Plasmapheresis Blood transfusion when necessary Disseminated intravascular coagulation Platelet transfusion Fresh frozen plasma Cryoprecipitate HELLP syndrome Immediate delivery of the baby Corticosteroids may be used Malignant hypertension Careful lowering of mean arterial pressure over 8 hours Parenteral antihypertensive agents such as labetalol, nicardipine, sodium nitroprusside etc Paroxysmal nocturnal hemoglobinuria Blood transfusions in severe anemia Prevention of thrombosis with warfarin Eculizumab

Do's

• Folic acid supplementation for all patients with hemolytic anemia.
• Erythropoietin decreases the need for transfusions, especially in children and patients with recurrent disease.
• Oral iron supplementation must be given in patients with iron deficiency.
• Corticosteroids whenever used, must be tapered. Most patients need low dose corticosteroid as a long term maintenance therapy.
• Vaccinate against influenza and encapsulated organisms like meningococcus and Streptococcus pneumoniae to prevent OPSI in patients who have undergone splenectomy.
• Long term monitoring of hemoglobin, reticulocyte count, LDH, bilirubin level and haptoglobin is needed to track response to therapy and future episodes of hemolysis.
• Transfusions must be avoided when not needed. When absolutely necessary, blood must be typed and matched. If in an emergency situation typing and cross matching is not possible, the least incompatible blood type is used to transfuse.
• Transfusion of blood must be done at a slow rate to prevent destruction of transfused RBCs.
• Treat iron overload with chelation therapy.
• Discontinue trigger medications such as penicillin or sulfa drugs.

Don'ts

• Do not transfuse blood in TTP/HUS as it increases risk of thrombosis.
• Corticosteroids must not be stopped abruptly. A tapered approach must be followed.

References