VA AM Report 12.8.17: Limitations of the blood smear & MAHA v2.0

Case summary: Our hearts exploded with happiness when our awesome ICU team presented a fascinating mystery case– a 54M with chronic low back pain and hypertension who presented with acute abdominal pain and was found to have anemia, thrombocytopenia and renal failure.

Top pearls:

  1. We discussed the limitations of smear and how obtaining a repeat smear, especially in cases where hemolysis is of persistent concern or where there are findings that might interfere with accuracy (e.g. other dysmorphic features that obscure schistocytes), can be useful diagnostically.
  2. The PLASMIC score (see Katie’s sick-nasty post on TTP and the PLASMIC score here) is a new diagnostic scoring system that can risk-stratify patients who should receive plasma exchange while awaiting ADAMTS13 results.
  3. Recall malignant hypertension as cause of MAHA!

Diagnostic approach to hemolytic anemia: stolen from one of my favorite Chief blogposts ever (no longer searchable?!) by the estimable Lekshmi Santhosh

RBC hemolysis results from damage to the RBC membrane. SEVERE damage leads to intravascular hemolysis. Less severe damage leads extravascular hemolysis.

  1. Intravascular hemolysis = RBCs lysed within the vasculature!

o   Causes include:

  • Shearing: MAHAs or defective mechanical heart valves
  • Complement mediated destruction: PNH, some drug reactions, ABO incompatibility, rarely AIHA from cold agglutins (IgM)
  • RBCs destroyed in the vasculature–>hemoglobinemia–>hemoglobinuria. NOT seen in extravascular hemolysis. Chronic heme loss in the urine leads to concomitant Fe deficiency anemia!

2. Extravascular hemolysis = RBCs destroyed/phagocytosed by macrophages in the liver, spleen, bone marrow, and lymph nodes.

o   Causes include:

  • Immune hemolytic anemia: RBCs coated in IgG, complement, or IgM+complement are phagocytosed in liver, spleen. Partial membrane phagocytosis–>microspherocytes! Coombs positive.
  • RBC membrane deformities: poorly deformable RBCs get stuck in sinusoids/cords of Billroth then phagocytosed. Ex: hereditary spherocytosis, G6PD def, thalassemia
  • All components of RBCs are recycled, including Fe, so you don’t get an Fe deficiency anemia

Hemolysis Labs – seen in intra and extravascular hemolysis

  • Reticulocyte count
  • Indirect bilirubin
  • Schistocytes on smear (in MAHAs)
  • Direct Antibody Test (Coombs): for immune mediated hemolytic anemia. Detects IgG or complement on RBCs. In IgM mediated hemolysis, will only detect complement bound to IgM, not the IgM itself!
  • LDH: released from lysed RBCs.
  • Free Hg binds to haptoglobin reducing its serum concentration.

o   Combo of increased LDH  + reduced haptoglobin = 90 percent specific for diagnosing hemolysis

o   Combo of a normal LDH + haptoglobin >25 mg/dL =  92 percent sensitive for ruling out hemolysis

Classic NEJM paper on blood smears: http://www.nejm.org/doi/full/10.1056/NEJMra043442#t=article


Malignant hypertension and hemolytic anemia

  • Just a reminder that malignant hypertension can mimic TTP/HUS, and distinguishing between the two is important because it guides therapy!
  • Pathophysiology: Malignant hypertension causes vascular wall damage, fibrin and platelet deposition in both the systemic and renal blood vessels. This luminal narrowing can lead to erythrocyte fragmentation and platelet destruction.
  • Overlap: Confusingly, TTP, HUS and atypical HUS can all be independently associated with hypertension, especially if there is severe renal dysfunction. In addition, malignant hypertension can mimic TTP/HUS, AND some case series have shown that even patients with low ADAMTS13 have ALTERNATIVE causes of their hemolysis

    Great TTP review: 

    George, J. (2010) How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 116: 4060–4069.

    TTP/HUS vs malignant hypertension:

    http://www.nature.com/articles/hr200512.pdf?origin=publication_detail

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