1/ #tweetorial #medstudenttwitter You are the admitting a a young female w/ paraesthesias and fatigue found to have a WBC 5.3, Hb 5.6 (MCV 110) and platelet count of 84k. Tbili is 2.1 (db .5), LDH 4579. Peripheral smear w/ schistocytes and macroovalocytes
2/What do you do next?
3/ The Plasmic score can be used in cases of suspected TTP to assess risk. Here the Plasmic score is 5 (making the assumption of ⬇️haptoglobin which is not reported) which is int risk. Heme consult+ADAMSTS13+eval for other etiologies.
4/ In this case (Source ncbi.nlm.nih.gov) plasmapheresis was initiated but platelets worsened to 42k after 4 days of Plex. Repeat evaluation showed low B12 levels and +IF antibody. Hb and platelets improved with B12 treatment.
5/Here we had a case of MAHA w/ schistocytes on peripheral smear w/ concern for TTP. Check out the @CPSolvers schema on MAHA. Coags were normal making DIC unlikely. (clinicalproblemsolving.com).
6/ In this case, the MCV was very ⬆️. In the Plasmic score, MCV <90 is more suggestive of TTP. Retics are about 8% larger than mature cells, so can see slightly elevated MCV w/ hemolysis, but unlikely to cause MCV of 110.
7/ B12 is important in DNA synthesis. In deficiency, nuclear division is impaired while cytoplasmic growth (relies on RNA) is less effected leading to large cells w/ hypersegmentation of nucleus. This causes intramedullary hemolysis which ⬆️LDH and other markers or hemolysis.
8/ It is an unusual in B12 def to have schistocytes on exam. One study observed this pseudothrombotic angiopathy in 2.5% of documented B12 deficiency. pubmed.ncbi.nlm.nih.gov. Since the hemolysis occurs in the bone marrow, likely not related to shearing like most MAHA cases.
9/ It is thought this may be due to hyperhomocysteinemia (pubmed.ncbi.nlm.nih.gov). Recall that ⬆️homocystein ⬆️ risk of thrombosis.
10/ So what are clues than can be used to differentiate pseudothrombotic angiopathy from TTP? In B12 deficiency that the bone marrow has difficulty producing mature cells leading to apoptosis. This leads to ⬇️ retic count (vs increased in TTP due to peripheral destruction).
11/ One study found that cases of pseudothrombotic angiopathy were associated w/ ⬇️ retic count, significant LDH⬆️, and severe anemia w/ mild to mod thrombocytopenia (pubmed.ncbi.nlm.nih.gov). Signs of hemolysis on labs w/ ⬇️ retic count, consider B12 def.
12/ An⬆️MCV and hypersegmented neutrophils can increase prob of B12 def, but absence should not exclude as sens of macrocytosis for B12 def is 30% in randomly screened pts w/ anemia & 75% in pts w/ anemia screened as part of diagnostic evaluation (pubmed.ncbi.nlm.nih.gov).
13/ In fact, I remember a morning report case about a pt who presented w/ psychosis w/ labs w/ anemia and severe thrombocytopenia. MCV normal in in high 80s. There was concern for TTP. Retic level was low. Diagnosis. B12 def.
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