Hemolytic anemia

General

• Wide variety of clinical presentation given the large differential diagnosis of Hemolytic Anemia
• Symptoms, Physical Exam, and Labs findings differ depending on intravascular vs. extravascular hemolysis, acute vs. chronic
• Common theme: low hemoglobin and hematocrit, reticulocytosis, elevated indirect bilirubin
• Most important lab to elucidate diagnosis is blood smear
• Divided by etiology: Acquired and Hereditary
  • Acquired:
    • Autoimmunity, microangiopathic, infection
  • Hereditary:
    • Sickle Cell Disease, Thalassemia, G6PD, Hereditary Spherocytosis
• Most common emergent presentations are due to acute intravascular hemolytic anemias

Clinical Features

History

• Anemia symptoms
  • Dyspnea
  • Fatigue
  • DOE
• Stigmata of intravascular hemolysis
  • Jaundice (new onset)
  • Dark urine
  • Changes in stool color
  • Neuro (TTP)
    • Headache
    • AMS
    • Seizure
    • Focal deficit
    • Coma
  • Rectal Bleeding (HUS)
• Stigmata of thrombocytopenia
  • Petechiae
  • Bleeding
• Stigmata of extravascular RBC destruction
  • Abdominal pain
  • Back pain
• Systemic Symptoms
  • Fevers
  • Night sweats
  • Weight loss
  • Confusion
• Other
  • Trauma
  • Initiation of new medication
  • Recent travel
  • Recent bug bites

PMH

• Hereditary Spherocytosis
• Sickle Cell Disease
• G6PD Deficiency recently started new medication:
  • Dapsone
  • Phenazopyridine
  • Nitrofurantoin
  • Primaquine
  • Rasburicase
  • Methylene blue
  • Tolonium chloride (toluidine blue)
• Malignancy
• Renal Failure
• Connective Tissue Disease
• Family history of Anemia/Bleeding

Physical Exam

• Cardiovascular
  • Tachycardia with flow murmur
  • Heart murmur – prosthetic heart valve
• Abdominal Exam
  • Hepatomegaly
  • Splenomegaly
  • Ascites
• Skin
  • Petechiae
  • Bruising
  • Lymphadenopathy
  • Brown recluse spider bites

Differential Diagnosis

Acquired Hemolytic Anemia

Microangiopathic Hemolytic Anemia

• HUS
• TTP
• DIC
• Malignant Hypertension

Autoimmune

• Warm Antibody Autoimmune Hemolytic Anemia

Infection

• Malaria
• Babesia

Other

• Brown recluse spider venom

Hereditary/Congenital Hemolytic Anemia

• G6PD – medication induced hemolytic anemia
• Sickle Cell Disease
• Thalassemia
• Hereditary Spherocytosis

Evaluation

• Labs
  • CBC
    • Look for low h/h
    • Low platelet count -> microangiopathic hemolytic anemia
  • Blood smear is one of the most important tests to obtain
  • Reticulocyte Count
  • CMP
    • Most important: indirect bilirubin and creatinine
  • UA, Urine Hemoglobin, Urine Hemosiderin, Upreg
  • PT/INR
  • Hemolysis Labs
    • LDH
    • Haptoglobin
    • Fibrinogen
  • Direct Anti-Globulin Test or Coombs test
  • If concern for Malaria:
    • Thick and Thin prep
    • Parasitemia
  • HIV
  • Blood cultures
  • Urine Cultures
  • Consider LP if neuro symptoms

Lab Interpretation

TABLE

Management

• ABC’s and Resuscitation if necessary
• 2 Large bore IVs
• Emergent hematology consultation if patient is very ill appearing

Acquired Hemolytic Anemia

Microangiopathic Hemolytic Anemia

• HUS
  • Supportive Care
    • Hydration
    • Pain control
  • Hemodialysis if acute renal failure
  • Do NOT give Antibiotics: results in increased expression of Shiga Toxin from E. Coli O157:H7

• TTP
  • Avoid platelet transfusion, except in life-threatening bleeding or intracranial hemorrhage
  • Plasma Exchange
  • If Plasma exchange cannot be performed immediately, give FFP and pheresis later.
  • Infusion with factor VIII concentrate

• DIC
  • Platelets if count is <50,000 and/or significant bleeding
  • pRBC if active bleeding or hemodynamically unstable
  • FFP if active bleeding
  • Cryoprecipitate if fibrinogen <150 and bleeding
  • TXA is only indicated for active or massive bleeding

• Malignant hypertension
  • Decreased blood pressure as clinically indicated

Autoimmune

• Warm Antibody Autoimmune Hemolytic Anemia
  • High-dose corticosteroids PO (1-2mg/kg per day for 3-4 weeks)
  • Monoclonal antibodies and immunosuppressive agents
  • Plasma exchange for severe hemolysis
  • Allogeneic RBC transfusion for life-threatening anemia

Infection

• Malaria
  • Visit CDC website to determine resistance pattern: https://www.cdc.gov/malaria/diagnosis_treatment/treatment.html
  • CDC Malaria Hotline: (770) 488-7788 or (855) 856-4713 toll-free Monday-Friday 9 am to 5 pm EST - (770) 488-7100 after hours, weekends and holidays

• Babesia
  • Mild/moderate Disease
    • Atovaquone 750mg PO q12hr plus Azithromycin 500mg PO on day 1, then 250mg/day PO
  • Severe Disease
    • Adult: Clindamycin 300-600mg IV qid or 600mg PO TID Plus Quinine 650mg PO TID x 7-10 days
    • Consider exchange transfusion if parasitemia >10%
  • Supportive treatment

Other

• Brown recluse spider venom
  • Supportive care
    • Hemodynamic support with fluids and pressers if necessary
    • Blood product transfusion if necessary

Hereditary/Congenital Hemolytic Anemia

• G6PD
  • Stop new medications
  • Treat any infections aggressively
  • Ovoid oxidant drugs
  • Blood transfusion if severe illness

• Sickle Cell Disease
  • Hemolytic anemia in SCD is typically chronic in nature not requiring treatment in the ED.
• Thalassemia
  • Hemolytic anemia in Thalassemia is typically chronic in nature not requiring treatment in the ED.
• Hereditary Spherocytosis
  • Hemolytic anemia in Hereditary Spherocytosis is typically chronic in nature not requiring treatment in the ED.

Disposition

Admit

References

• Dhaliwal G, Cornett P, Tierney LM Jr. Hemolytic Anemia. Am Fam Physician. 2004 Jun 1;69(11):2599-606.
• Rother RP, Bell L, Hillmen P, Gladwin MT. The Clinical Sequelae of Intravascular Hemolysis and Extracellular Plasma HemoglobinA Novel Mechanism of Human Disease. JAMA. 2005;293(13):1653-1662. doi:10.1001/jama.293.13.1653
• Barcellini W, Fattizzo B. Clinical applications of hemolytic markers in the differential diagnosis and management of hemolytic anemia. Disease markers. 2015 Dec 27;2015.
• Bain BJ. Diagnosis from the blood smear. New England Journal of Medicine. 2005 Aug 4;353(5):498-507.
• Tefferi A. Anemia in adults: a contemporary approach to diagnosis. In Mayo Clinic Proceedings 2003 Oct 31 (Vol. 78, No. 10, pp. 1274-1280). Elsevier.
• Wada H, Matsumoto T, Yamashita Y. Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines. Journal of Intensive Care. 2014;2(1):15. doi:10.1186/2052-0492-2-15.
• McDade, Jenny et al. Brown Recluse Spider (Loxosceles reclusa) Envenomation Leading to Acute Hemolytic Anemia in Six Adolescents. The Journal of Pediatrics, Volume 156, Issue 1, 155 - 157
• Albert E. Anderson, Paul B. Cassaday, George R. Healy. Babesiosis in Man: Sixth Documented Case American Journal of Clinical Pathology Nov 1974, 62 (5) 612 618; DOI:10.1093/ajcp/62.5.612