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Heparin-induced thrombocytopenia (HIT) [1].


Heparin-induced thrombocytopenia (HIT) is the development of thrombocytopenia (low platelet counts) due to the administration of heparin, either in its "unfractionated" or "low molecular weight" form. HIT may affect up to 3% of patients exposed to heparin.  HIT is very rare in patients treated with low molecular weight heparin (LMWH). More than half of the patients with asymptomatic HIT  may experience formation of abnormal blood clots in the following 30 days. 

There are two types of HIT:

Type I occurs within a few days of heparin exposure. Self limited and benign.

Type II occurs from 5 days to 3 weeks after starting treatment. Autoimmune immunoglobulin-mediated syndrome associated with venous and arterial thrombosis.

Although the diagnosis of HIT is made primarily on clinical grounds laboratory tests such as the heparin/PF 4 ELISA, heparin-induced platelet aggregation (HIPA), and the serotonin release assay (SRA) are used to help confirm the diagnosis.

The Pregnancy and Thrombosis Working Group recommends that if the platelet count drops below 150,000 or 50% from baseline during  heparin or LMWH therapy, it is recommended to stop heparin including IV flushes. It is recommended that patients diagnosed with HIT should have consultation with a hematologist and be treated with fondaparinux [1].


Fondaparinux sodium (Arixtra ®)
Synthetic and specific inhibitor of activated Factor Xa.
Molecular weight = 1728
 

  • Prophylaxis (no active clot)[1]

         2.5 mg subcutaneous injection once daily
     

  • Therapeutic (active thrombosis) [1]

    Less than 50 kg

         5 mg subcutaneous injection once daily

    50 to 100 kg

         7.5 mg subcutaneous injection once daily

    Greater than 100 kg

         10 mg subcutaneous injection once daily

 

ARIXTRA Injection is contraindicated in patients with severe renal impairment (creatinine clearance < 30 mL/min), active major bleeding, bacterial endocarditis, in patients with thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux sodium, or in patients with known hypersensitivity to fondaparinux sodium.
 

When epidural/spinal anesthesia or spinal puncture is employed, patients anticoagulated or scheduled to be anticoagulated with low—molecular-weight heparins, heparinoids or fondaparinux sodium are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis.


(2.5 mg, 5mg, 7.5 mg, 10 mg  single dose prefilled syringes)


Fondaparinux has been reported to cross over to the fetus in small amounts. Although the dose appears to be below the concentration that effectively thins the blood potentially hazardous effect cannot be ruled out. The authors of this report suggested that the use of Axitra in pregnant women "might best be limited to those for whom there are no obvious therapeutic alternatives, such as patients with heparin induced thrombocytopenia or severe allergic reactions to heparin ".

Fondaparinux sodium was found to be excreted in the milk of lactating rats. However, it is not known whether this drug is excreted in human milk.
 

REFERENCES

1. Duhl AJ et. al Antithrombotic therapy and pregnancy: consensus report and recommendations for the prevention of venous thromboembolism and adverse pregnancy outcome. Am J Obstet Gynecol 2007;197:147.e1-457.e21 PMID:17980177

2. Dempfle CE. Minor transplacental passage of fondaparinux in vivo. N Engl J Med. 2004 Apr 29;350(18):1914-5. PMID:15115845
 

 

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