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Drug-Induced Thrombocytopenia
Low Blood Platelet Count due to Drugs

Drug-induced thrombocytopenia is a rare immune-mediated reaction in which platelet destruction is induced by several mechanisms, most important being bone marrow suppression and/ or antibody formation. The clinical presentation depends on the severity of thrombocytopenia, ranging from mild ecchymoses and petechiae to life-threatening central nervous system or gastrointestinal bleeding. After confirming low platelet count in blood work, a thorough patient history is essential to identify the drug responsible for thrombocytopenia.

Presentation

Drug-induced thrombocytopenia is an uncommon phenomenon characterized by a reduced platelet count (< 50×10^9/L) after the use of various drugs [1] [2] [3] [4]. Quinine, quinidine, antibiotics (trimethoprim-sulfamethoxazole, vancomycin, linezolid, rifampin, ceftriaxone and penicillins), antiepileptic drugs (carbamazepine), glycoprotein IIb/IIIa inhibitors (abciximab and eptifibatide), cytotoxic agents, and heparin are described as some of the most common drugs known to cause thrombocytopenia in the literature [4] [5] [6]. Signs and symptoms, in the form of bleeding disorders, usually start at least one week after drug use [3] [4] [5]. Some drugs, however, such as abciximab, can induce the formation of drug-dependent antibodies within hours [5]. In patients with milder thrombocytopenia, principal signs include petechiae, epistaxis, ecchymoses, bruising, and mucosal bleeding, seen in up to two-thirds of patients [2] [4]. On the other hand, severe gastrointestinal bleeding, hematuria, purpura of the skin and mucosal surfaces, but also intracranial hemorrhage that may be life-threatening, are reported in the case of severe thrombocytopenia (< 10x109/L) [4] [7]. With the cessation of the offending drug, signs, and symptoms might completely disappear within a few days, but in the absence of an early diagnosis, fatal hemorrhage can occur [3] [4].

Skin

  • Purpura

    DIT can be distinguished from idiopathic thrombocytopenic purpura, a bleeding disorder caused by thrombocytopenia not associated with a systemic disease, based on the history of drug ingestion or injection and laboratory findings. [ncbi.nlm.nih.gov]

    ( D47.3 ) purpura fulminans ( D65 ) thrombotic thrombocytopenic purpura ( M31.1 ) Waldenström hypergammaglobulinemic purpura ( D89.0 ) Purpura and other hemorrhagic conditions D69.5 ICD-10-CM Diagnosis Code D69.5 Secondary thrombocytopenia 2016 2017 [icd10data.com]

    Increased destruction of platelets can be caused by infections, certain drugs, transfusion-related purpuras, idiopathic thrombocytopenic purpura, and disseminated intravascular coagulation. adj., adj thrombocytope´nic. Patient Care. [medical-dictionary.thefreedictionary.com]

    MDS) *TTP/HUS = Thrombotic thrombocytopenic purpura/Hemolytic Uremic Symptom Table 5. [antimicrobe.org]

Workup

The sudden onset of symptoms related to bleeding disorders must raise suspicion toward an iatrogenic cause [1]. Many authors have stressed the pivotal role of a properly obtained patient history to confirm whether prescribed drugs are responsible for the presenting signs and symptoms [1] [3] [5]. Physicians must perform a meticulous examination of the skin and mucosal tissues, and laboratory studies to confirm thrombocytopenia [1] [3] [5]. The severity of bleeding manifestations often (but not always) correlate with the degree of thrombocytopenia, and levels as low as 1x109/L have been documented [4]. Additional laboratory tests that should be done are a full coagulation panel, fibrinogen, D-dimer, bilirubin, lactate dehydrogenase (LDH), haptoglobin, hematocrit, and a peripheral blood smear which is highly useful as well [7]. Once a preliminary diagnosis is made, more advanced studies can be implemented in order to confirm the presence of drug-dependent antibodies (DDAs) [2]. Various techniques are used, including enzyme-linked immunoassay (ELISA), flow cytometry and Western blotting (WB), to confirm the diagnosis [2] [5] [6]. However, due to the cost and the paucity of advanced laboratories with these methods throughout the world, drug-induced thrombocytopenia is often diagnosed based on clinical findings [1] [4].

Treatment

IVIG treatment partially prevented platelet clearance by DITP and ITP antibodies. [ncbi.nlm.nih.gov]

She received oral treatment with naproxen, ondansetron and omeprazol. Platelet count was 328 000 × 10 9 /l at the start of treatment. [academic.oup.com]

On the fourth day of IVIG treatment, the patient developed right thalamic lacunar infarction. The IVIG treatment was continued for 4 weeks along with bivalirudin. [karger.com]

Measures of treatment effect According to the recommendations in Chapter 9 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011), we used the following measures of the effects of treatment. [cochranelibrary.com]

Prognosis

Thrombocytopenia generally resolves quickly after offending medication withdrawal, and the prognosis of drug-induced thrombocytopenia is then excellent. [ncbi.nlm.nih.gov]

(Outcomes/Resolutions) The prognosis of Drug-Induced Thrombocytopenia is usually excellent, if the drug causing the condition is identified and discontinued, when possible In some, the prognosis may get complicated, if there is large amount of bleeding [dovemed.com]

Prognosis The prognosis is very variable and will depend on the underlying condition. [patient.info]

Prognosis Thrombocytopenia can result in fatal bleeding, but it also can indicate various other, more serious, cancers and disorders that affect the blood cells. This condition requires thorough medical evaluation. [medical-dictionary.thefreedictionary.com]

Etiology

Abstract Although drugs are a common cause of acute immune-mediated thrombocytopenia in adults, the drug etiology is often initially unrecognized. [ncbi.nlm.nih.gov]

Future patient case reports should incorporate standard criteria to clearly establish the etiologic role of the drug. [annals.org]

OBJECTIVE: To assess etiology and impact of thrombocytopenia in a large oral glycoprotein (GP) IIb/IIIa inhibitor trial. BACKGROUND: Heparin is known to cause thrombocytopenia, and in some of these patients thrombosis. [timi.org]

Epidemiology

In this chapter, we review current knowledge about the pathophysiology, epidemiology, clinical manifestations, and treatment of HIT in the intensive care unit (ICU). [ccforum.biomedcentral.com]

EDTA-dependent pseudothrombocytopaenia: a 12-month epidemiological study. Scand J Clin Lab Invest. 1988;48(6):537–542. 18. Sane DC, Damaraju LV, Topol EJ, et al. [aafp.org]

Thiolliere F, Serre-Sapin AF, Reignier J, Benedit M, Constantin JM et al. (2013) Epidemiology and outcome of thrombocytopenic patients in the intensive care unit: results of a prospective multicenter study. [journals.plos.org]

Pathophysiology

We also provide a brief review of the literature and comment on the pathophysiology of this rare condition. [ncbi.nlm.nih.gov]

Fondaparinux-associated Thrombocytopenia Pathophysiology Since fondaparinux is a heparin-like drug, an interesting question is, “Can fondaparinux cause HIT?” [hematologyandoncology.net]

Pathophysiology of ITP – Intevention Areas 78. [slideshare.net]

Table 1: Naranjo ADR probability scale-items and score and the present case Click here to view The miscellaneous pathophysiologic mechanisms of drug-induced thrombocytopenia can be divided into two major categories : Decreased platelet production via [mjdrdypu.org]

N/A Pathophysiology Thrombocytopenia may be due to many causes. The etiology can be anticipated by the history. [oncologynurseadvisor.com]

Prevention

For Part 1 population (to prevent CIT) and Part 2 population (to prevent recurrence of CIT) and other, one awaiting classification trial involving 75 participants was found. [cochranelibrary.com]

IVIG treatment partially prevented platelet clearance by DITP and ITP antibodies. [ncbi.nlm.nih.gov]

The Heart Outcomes Prevention Evaluation Study investigators. N Engl J Med 2000;342: 145-153. ‏ الصفحة 468 - Antiplatelet Trialists' Collaboration. [books.google.com]

Additionally, treatment measures including platelet transfusion, plasmapheresis, and corticosteroid medication may be required, in some cases of severe hemorrhage, to bring platelet count to normal range and prevent further bleeding episodes The prognosis [dovemed.com]

It is important to make sure that you're taking enough medicine to prevent clots, but not so much that it causes bleeding. [icdlist.com]

References

  1. Aster RH, Curtis BR, McFarland JG, Bougie DW. Drug-Induced Immune Thrombocytopenia: Pathogenesis, Diagnosis, and Management. J Thromb Haemost. 2009;7(6):911-918.
  2. Visentin GP, Liu CY. 9. Drug-Induced Thrombocytopenia. Hematol Oncol Clin North Am. 2007;21(4):685-vi.
  3. George JN, Aster RH. Drug-induced thrombocytopenia: pathogenesis, evaluation, and management. Hematology Am Soc Hematol Educ Program. 2009;153-158.
  4. Rondina MT, Walker A, Pendleton RC. Drug-Induced Thrombocytopenia for the Hospitalist Physician with a Focus on Heparin-induced Thrombocytopenia. Hosp Pract (1995). 2010;38(2):19-28.
  5. Arnold DM, Nazi I, Warkentin TE, et al. Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia. Transfusion medicine reviews. 2013;27(3):137-145.
  6. Arnold DM, Kukaswadia S, Nazi I, Esmail A, Dewar L, Smith JW, et al. A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia. J Thromb Haemost. 2013;11:169–176.
  7. Kenney B, Stack G. Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009;133(2):309–314.
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