Hemolytic anemia
Background
- Wide variety of clinical presentation given the large differential diagnosis
- Clinical presentation and lab findings differ depending on intravascular vs. extravascular hemolysis, acute vs. chronic
- Common findings
- low hemoglobin and hematocrit
- reticulocytosis
- elevated indirect bilirubin
- Most important lab to elucidate diagnosis is blood smear
- Most common emergent presentations are due to acute intravascular hemolytic anemias
Etiologies
Divided by etiology: acquired vs. hereditary
- Acquired:
- Microangiopathic (MAHA), autoimmune, infection
- Hereditary:
Clinical Features
History
- Anemia symptoms
- Dyspnea/dypsnea on exertion
- Fatigue
- Stigmata of intravascular hemolysis
- Jaundice (new onset)
- Dark urine
- Changes in stool color
- Neuro (TTP)
- Rectal bleeding (HUS)
- Stigmata of thrombocytopenia
- Petechiae
- Bleeding
- Stigmata of extravascular RBC destruction
- Systemic Symptoms
- Fever
- Night sweats
- Weight loss
- Confusion
- Other
- Trauma
- Initiation of new medication
- Recent travel
- Recent insect 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
Autoimmune
Infection
Other
Hereditary/Congenital Hemolytic Anemia
- G6PD – medication induced hemolytic anemia
- Sickle cell disease
- Thalassemia
- Hereditary spherocytosis
Evaluation
Workup
- CBC
- Low hemaglobin/hematocrit
- Low platelet count → microangiopathic hemolytic anemia
- Blood smear
- Reticulocyte count
- CMP
- Most important: indirect bilirubin and creatinine
- UA (for hemoglobin, hemosiderin), uHCG
- 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
Microangiopathic Hemolytic Anemia | H/H | Platelets | Indirect Bili | Creatinine | Blood Smear | PT/INR | LDH | Haptoglobin | Fibrinogen | DAT/Coombs Test | Thick/Thin Prep |
HUS | low | low | elevated | highly elevated | schistocytes | wnl | elevated | low | wnl | negative | negative |
TTP | low | low | elevated | elevated | schistocytes | wnl | elevated | low | wnl | negative | negative |
DIC | low | low | elevated | elevated | schistocytes | elevated | elevated | low | low | negative | negative |
Malignant Hypertension | low | low | elevated | variable | schistocytes | elevated | low | negative | negative | ||
Autoimmune | H/H | Platelets | Indirect Bili | Creatinine | Blood Smear | PT/INR | LDH | Haptoglobin | Fibrinogen | DAT/Coombs Test | Thick/Thin Prep |
Warm Antibody AHA | low | wnl | elevated | spherocytes | elevated | low | wnl | positive | negative | ||
Infection | H/H | Platelets | Indirect Bili | Creatinine | Blood Smear | PT/INR | LDH | Haptoglobin | Fibrinogen | DAT/Coombs Test | Thick/Thin Prep |
Malaria | low | wnl | elevated | see thick/thin prep | variable | elevated | low | wnl | negative | paracytes | |
Babesia | see thick/thin prep | negative | paracytes | ||||||||
Other | H/H | Platelets | Indirect Bili | Creatinine | Blood Smear | PT/INR | LDH | Haptoglobin | Fibrinogen | DAT/Coombs Test | Thick/Thin Prep |
Brown recluse | low | wnl | elevated | elevated | positive | negative |
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
- Supportive Care
- TTP
- Avoid platelet transfusion, except in life-threatening bleeding or intracranial hemorrhage
- Plasma exchange
- If Plasma exchange cannot be performed immediately, give FFP and plasmapharese later.
- Factor VIII concentrate
- DIC
- Platelet transfusion 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
- Reduce 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
- Babesiosis
- Mild/moderate Disease
- Atovaquone 750mg PO q12hr AND
- Azithromycin 500mg PO on day 1, then 250mg/day PO
- Severe Disease
- Clindamycin 300-600mg IV QID OR 600mg PO TID AND
- Quinine 650mg PO TID x7-10 days
- Consider exchange transfusion if parasitemia >10%
- Supportive treatment
- Mild/moderate Disease
Other
- Brown recluse spider bite
- Supportive care
- Hemodynamic support with fluids and pressers if necessary
- Blood product transfusion if necessary
- Supportive care
Hereditary/Congenital Hemolytic Anemia
- G6PD
- Stop new medications
- Treat any infections aggressively
- Ovoid oxidant drugs
- Blood transfusion if severe illness
- Sickle Cell Disease, Thalassemia, Hereditary spherocytosis
- Hemolytic anemia in the above diseases typically chronic, usually does not require treatment in ED
Disposition
- Depends on severity, complications, etc.