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Case Report - (2019) Volume 10, Issue 1

Heparin Induced Thrombocytopenia in a Patient with Antiphospholipid Syndrome

Rabia Ahmad* and Sidra Chaudhry
Department of Pathology, Allama Iqbal Medical College, Lahore, Pakistan
*Corresponding Author: Rabia Ahmad, Department of Pathology, Allama Iqbal Medical College, Lahore, Pakistan, Tel: +923334267012 Email:

Abstract

Heparin-induced thrombocytopenia (HIT) is a less commonly encountered adverse reaction of heparin characterized by formation of heparin complex with platelet factor 4 due to formation of autoantibody. HIT is reported in about 2% of all patients receiving heparin, out of which 35% develop thrombosis. In Antiphospholoipid syndrome autoantibodies are generated to phospholipid binding proteins which are risk factors for thrombosis and pregnancy complications. In this report we present case of a patient with recurrent venous thromboembolism receiving heparin and was found to develop HIT with coexistence of Antiphospholipid syndrome.

Keywords: Thrombosis; Platelet; Pregnancy; Antibodies; Pulmonary embolismAbbreviations: DVT: Deep Vein Thrombosis; PE: Pulmonary Embolism; APS: Antiphopholipid Syndrome; HIT: Heparin Induced Thrombocytopenia

Case Report

A 30-year-old female with history of recurrent episodes of deep venous thrombosis and pulmonary embolism presented with painful left lower extremity swelling. She was receiving low molecular heparin at the time of presentation. Physical examination of the affected lower limb showed a swollen, mildly tender, and warm whole left lower limb. There was mild tachycardia and tachypnea as well. Lower extremity doppler ultrasonography revealed an occlusive venous thrombosis (DVT) extending to calf veins from femoral veins. There was previous history of repeated hospital admissions for deep vein thrombosis and pulmonary embolism. Patient previously received low molecular weight heparin and direct oral anticoagulants with partial improvement. A high resolution computed tomography of the chest with contrast showed embolus in subsegmental branches of right pulmonary artery. Patient was receiving low molecular weight heparin, which was withheld and intravenous heparin was started. While receiving unfractionated heparin, full blood counts were done which revealed reduction of platelet counts to 30000/μl on 5th day with initial platelet count of 200000/μl. Patient developed right-sided pleuritic chest pain. There was extension of deep vein thrombosis in lower limb up to left internal iliac vein. Pretest probability revealed a score of 5 which accounts for intermediate probability of heparin induced thrombocytopenia (HIT). Heparin was stopped, and due to nonavailability of Enzyme-linked immunosorbent assays (ELISA) for heparin induced thrombocytopenia, patient was started on alternate anticoagulant i.e, fondaparinux 7.5 mg subcutaneously and monitoring with serial venous duplex ultrasound was continued. Due to nonavailability of FDA approved medicines for heparin induced thrombocytopenia (HIT) like argatroban and danaproid, we chose fondaparinux. Continuous oxygen inhalation was given throughout. Three days after starting fondaperinux, partial recanalization of lower limb deep vein thrombosis within the left external iliac vein and the left femoral popliteal system was clearly demonstrated. After 10 days of starting fondaparinux, the platelet count raised up to 100 x 109/L and she was maintaining her oxygen saturation at 97% with 2 L/ min.Antiphospholipid antibody profile demonstrated elevated anti-β2 glycoprotein 1 and anticardiolipin. Once platelet count improved and DVT recanalization was achieved, warfarin was started (Figure 1 and Table 1) Warfarin was overlapped with fondaparinux for 4 days after INR reached 2.5. Three months after the initial diagnosis, antiphospholipid antibodies levels were still elevated, confirming the diagnosis of antiphospholipid syndrome (APS). Patient had no history of miscarriage or recurrent pregnancy loss. She had one alive issue. We discussed about pregnancy complication with patient and avoiding heparin during pregnancy and the risk of fetal toxicity with warfarin. Patient decided to avoid pregnancy in future.

blood-disorders-transfusion-Heparin-Thrombocytopenia

Figure 1: HIT: Heparin-Induced Thrombocytopenia; ELISA: Enzyme-Linked Immunosorbent Assay; OD: Optical Density; HIPA: Heparin-Induced Platelet Aggregation; SRA: Serotonin Release Assay; PLT: Platelet Count; DIC: Diseminated Intravascular Coagulation.
*Clinical judgement is required to assess the likelihood of another cause for thrombocytopenia; thus, there may be extremely rare cases in which an individual with a low -probability 4 ts score has HIT.

4 Ts Parameters:
Thrombocytopenia:
PLT decreases >50% BUT AND nadir  ≥ 20,000/microl AND no surgery within preceding 3 days 2 Points
PLT decreases >50% BUT surgery within preceding 3days OR any combination of PLT fall and nadir that does not fit criteria for 2 or 0 points (eg, 30 to 50%^fall or nadir 10,000 to 19,000/microl) 1 Points
PLT decrease <30% Ornadir <10,000/microl 0 Points
Timings of onset after heparin exposure:
5 to 10 days OR 1 day if exposure within past 5 to 30 days 2 Points
Propable 5 to 10 days ( eg, missing PLT counts)OR 1 Points
>10 days OR,1 days f exposue within past 100 days 0 Points
Thrombosis or other clinical sequelae:
confirmed new thrombosis, skin necrossis, anaphylactoid reaction, or adrenal hemorrhage 2 Points
Suspected, progressive, or recurrent thrombossis, skin erythema 1 points
None 0 Points
Other cause for the thrombocytopenia:
None 2 Points
Possible (eg, sepsis) 1 points
Probable(eg,DICmedication, within 72 hours of surgery) 0 Points
Interpretation:
0 to 3 points- Low probability
4 to 5 points- intermediate probability
6 to 8 - High probability
For patients receiving warfarin who do not have a thrombosis, warfarin should be withheld until stable anticoagulation has been achieved; for those with HIT who have a thrombosis while receiving warfarin, the warfarin should be reversed with vitamin K and held until stable coagulation has been achieved. Options for anticoagulation in HIT include argatroban, bivalirudin, danaparoid, fondaparinux, or a direct oral anticoagulant (dabigatran, apixaban, rivaroxaban, edoxaban). Refer to the up to date table on selection of non-heparin anticoagulants in HIT for important considerations related to administration route, half-life, use in renal and hepatic failure, and monitoring. Warfarin can be used after the appropriate duration of intial anticoagulation, anticoagulation as it is expected to resolve rapidly upon heparin discontinuation. The specific testing needed depends on availability and turnaround time of an ELISA-type immunoassay and a gold standard test (HIPA or SRA). Refer to uptodate for the optimal sequence and interpretation of testing. If the ELISA result is between 0.40 and 1.00, a gold standard test should be performed

Table 1: 4 Ts score Parameters

Discussion

Usually Antiphospholipid syndrome and heparin-induced thrombocytopenia don’t coexist. There is no such case reported from our country previously. Another feature is a unique presentation as this patient received low molecular weight heparin off and on previously during hospitalization as well but developed HIT on receiving unfractionated heparin.

A similar case was reported by Tun et al. in which a 42-year-old female developed pulmonary embolism, superior mesenteric artery thrombosis, and had thrombocytopenia and positive HIPA. However, serotonin release assay was not reported [1].

Another study also suggests that APS may increase predisposition to HIT [2].

A retrospective study reported that out of 20 patients with primary APS, 07 developed HIPA. Two of the seven patients had positive aggregation tests for HIT [3]. Another study proposed that, the vascular endothelium seen in APS leads to exposure of glycosaminoglycans such as heparin sulphate that may complex with platelet factor 4. This may cause molecular modification that produces neoantigens and HIPA [4-6].

Similarly, there are two other reported cases of HIT in patients with APS who had thrombosis but negative HIPA. So, presence of APS antibodies may interfere with HIT diagnostic tests [7,8].

In a patient with both HIT and APS, the 14th international congress on APS task force suggests anticoagulation with argatroban or danaparoid. The use of danaparoid has been discontinued in the United States. There are four other case reports in the literature, detailing the successful use of fondaparinux in patients with concurrent APS and HIT. Our case further favors use of fondaparinux in venous thromboembolism with HIT and APS [9-10].

There is genetic predisposition for formation of HIT antibody in patients having prothrombin G20210 A polymorphism [2].

Conclusion

In patients with APS, thrombocytopenia developed or increased during heparin therapy should be investigated for HIT antibody. Timely diagnosis and prompt treatment can prevent morbidity and mortality. It is also suggested that in this era of modern medicine, the multidisciplinary approach to diagnose HIT must be appreciated.

References

  1. Tun NT, Krishnamurthy M, Snyder R (2015) Catastrophic antiphospholipid syndrome and heparin-induced thrombocytopenia-related diseases or chance association? BLOOD COAGUL FIBRIN 26: 214-219.
  2. Lasne D, Saffroy R, Bachelot C, Vincenot A, Rendu F, et al. (1997) Tests for heparin-induced thrombocytopenia in primary antiphospholipid syndrome. Br J Haematol 97: 939.
  3. Martinuzzo ME, Forastiero RR, Adamczuk Y, Pombo G, Carreras LO, et al. (1999) Antiplatelet factor 4-heparin antibodies in patients with antiphospholipid antibodies. Thromb Res 95: 271-279.
  4. Hoppensteadt, Debra A, Walenga JM (2008) The relationship between the antiphospholipid syndrome and heparin-induced thrombocytopenia. Hematol Oncol Clin North Am 22: 1-18.
  5. Martin-Toutain I, Piette JC, Diemert MC, Faucher C, Jobic L, et al. (2007) Hgh prevalence of antibodies to platelet factor 4 heparin in patients with antiphospholipid antibodies in absence of heparin-induced thrombocytopenia. Lupus 16: 79-83.
  6. I, et al. (2008). Anti-heparin platelet factor 4 antibodies in systemic lupus erythaematosus are associated with IgM antiphospholipid antibodies and the antiphospholipid syndrome. Ann Rheum Dis 67: 395-401.
  7. Perunicic J, Antonijevic NM, Miljic P, Djordjevic V, Mikovic D, et al. (2008) Clinical challenge: Heparin-induced thrombocytopenia type II (HIT II) or pseudo-HIT in a patient with antiphospholipid syndrome. J Thromb Thrombolysis 26: 142-146.
  8. Zeller L, Almog Y, Tomer A, Sukenik S, Abu-Shakra M, et al. (2006) Catastrophic thromboses and severe thrombocytopenia during heparin therapy in a patient with anti-phospholipid syndrome. Clin Rheumatol 25: 426-429.
  9. Warkentin TE, Pai M, Sheppard JI, Schulman S, Spyropoulos AC, et al. (2011) Fondaparinux treatment of acute heparin‐induced thrombocytopenia confirmed by the serotonin‐release assay: a 30‐month, 16‐patient case series. J Thromb Haemost 9: 2389-2396.
  10. Holtan SG, Knox SK, Tefferi A (2006) Use of fondaparinux in a patient with antiphospholipid antibody syndrome and heparin-associated thrombocytopenia. J Thromb Haemost 4: 1632-1634.
Citation: Ahmad R, Chaudhry S (2018) Heparin Induced Thrombocytopenia in a Patient with Antiphospholipid Syndrome. J Blood Disord Transfus 10:411.

Copyright: © 2018 Ahmad R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.