ITP: Treatment with Anti-Rh(D) Globulin

Thank you to Dr. Chesteen for an interesting case today of an older gentleman with HCV cirrhosis who developed an acute platelet drop while hospitalized. It brought up discussion of the differential for thrombocytopenia and the management of immune thrombocytopenic purpura (ITP) specifically highlighting the use of anti-Rh(D) globulin.

 Where did all the platelets go?

Where did all the platelets go?

Thrombocytopenia causes are extensive. But, there are a few large categories to think about to make it simpler. One system is based on where the platelet issue is happening: bone marrow disorders, platelet destruction/consumption, dilution or redistrubution/splenomegaly. Another approach is based on etiology itself.

  • Pseudothrombocytopenia: are they falsely low? Look at the peripheral smear for clumping or giant platelets.
  • Primary Immune Thrombocytopenia (ITP):
  • Secondary Thrombocytopenia:
    • Drug Induced: heparin, quinine, sulfa, APAP, cimetidine, NSAIDs, antibiotics, GPIIa-IIIb inhibitors, alcohol
    • Infections: HIV, HCV, EBV, H.pylori, sepsis/DIC, intracellular parasites -> TTP, HUS, DIC
    • Hyperspleenism
    • Nutrient Deficiencies: vitamin B12, folate, copper
    • Rheumatologic/Autoimmune: SLE, RA
    • Pregnancy: gestational, preeclampsia, HELLP syndrome
    • Malignancy: bone marrow suppression, leukemia, cancer infiltration or malignancy itself-> DIC
  • Bone Marrow Driven: myelodysplasia, aplastic anemia:
  • Paroxysmal Nocturnal Hemoglobinuria (PNH):
  • Antiphospholipid Syndrome (APS):
  • Inherited: Von Willebrand disease, Wiskott-Aldrich syndrome, Alport syndrome, May-Hegglin anomaly, Fancomi syndrome, Bernard-Soulier syndrome, thrombocytopenia absent radius syndrome

Testing:

  • CBC + peripheral smear (schistoscytes = MAHA: DIC, TTP, HUS; nucleated RBC or Howell-Jolly = post-splenectomy; spherocytes = immune mediated, hereditary spherocytosis; leukoerythroblasts, teardrop cells, immatures = bone marrow process; hypersegmented PMNs = megalodysplastic syndrome)
  • HIV, HCV testing
  • Others based on clinical suspicion: LFTs, DIC panel (PT, aPTT, fibrinogen, LDH)

Idiopathic/Immune Thrombocytopenic purpura (ITP) Treatment: Goal of ITP treatment is to maintain a safe platelet count to prevent clinically relevant bleeding. The goal is NOT to normalize the platelet count. Generally, bleeding risk is low unless the platelets are less than 10,000 per microL. There is greater risk of bleeding with history of prior bleeds and older age. Below is a treatment algorithm proposed by UpToDate.

ITP therapy algorithm.JPG

A few comments on Rho(D) Globulin (WinRho[IV] or RhoGAM [IM]). It can be utilized if there is a spleen present and the patient is Rh+. The mechanism is via opsonization of endogenout Rh(D)+ RBCs with anti-Rh(D) resulting in preferential clearance by the RES thus, allowing Ab-coated platelets to remain in circulation. This is similar mechanistically to the use of IVIg. In the 2011 ASH ITP Pocket-Guide, first line therapy is listed as observation, corticosteroids, IVIg or anti-D immunoglobulin in spedific patients. The risk with anti-D is severe hemolysis. There is a black box warning for intravascular hemolysis, acute respiratory failure and DIC. Based on a 2012 Transfusion publication by an expert panel looking at a disproportionality analysis of the data, it was concluded that older individuals and those with other comorbidities (listed as EBV, HCV, AIHA, CKD, APLA, lymphoma or CLL) were are highest risk of a hemolytic reaction or death. If anti-D is to be used for ITP one should monitor baseline, after 2 hours and and 4 hours urinarlysis looking for hemoglobinuria. If there is evidence of back pain, fevers, chills or discolored urine, a complete evluation for intravascular hemolysis should be undertaken.

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