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Drug-induced Thrombocytopenia

Drug Induced Thrombocytopenia

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].

Easy Bruising
  • bruising Pinpoint red spots on the skin ( petechiae ) The first step is to stop using the medicine that is causing the problem.[medlineplus.gov]
  • bruising Pinpoint red spots on the skin ( petechiae ) Treatment The first step is to stop using the medicine that is causing the problem.[mountsinai.org]
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]
  • The patient presented with acute severe infusion reaction after the third treatment with natalizumab, developing whole-body purpura.[ncbi.nlm.nih.gov]
  • Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due to the difficult initial differentiation between the two conditions.[ncbi.nlm.nih.gov]
  • 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]
  • Severely affected individuals have florid purpura and bleeding from nose, gums and gastrointestinal or urinary tract.[clinlabnavigator.com]
Emotional Lability
  • Common side effects include dizziness, asthenia, tremor, diarrhea, nervousness, depression, and emotional lability. 1 No clinically relevant hematologic effects have been reported. 2 We describe a case of severe thrombocytopenia associated with tiagabine[neurology.org]
Agitation
  • Propofol, along with dexmedetomidine are preferred over benzodiazepines in mechanically ventilated ICU patients according to the SCCM Pain, Agitation, and Delirium guidelines (class 2B recommendation).[pharmacyjoe.com]

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]
  • Diagnostic methods and treatment are also summarized.[ncbi.nlm.nih.gov]
  • The patient presented with acute severe infusion reaction after the third treatment with natalizumab, developing whole-body purpura.[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]
  • The standard treatment was corticosteroids, which were administered in 53% of the cases. No difference in recovery between corticosteroid-treated and untreated patients was observed. No other clinical parameter affected the recovery rate.[ncbi.nlm.nih.gov]

Prognosis

  • Thrombocytopenia generally resolves quickly after offending medication withdrawal, and the prognosis of drug-induced thrombocytopenia is then excellent.[ncbi.nlm.nih.gov]
  • Once the offending agent has been discontinued, the overall prognosis is excellent. In the case of suspected or confirmed heparin-induced thrombocytopenia, an alternative anticoagulant should be initiated.[ncbi.nlm.nih.gov]
  • 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]
  • Prognosis The prognosis is very variable and will depend on the underlying condition.[patient.info]
  • Thrombocytopenia and prognosis in intensive care. Critical Care Medicine. 2000;28(6):1871-6. [PubMed] 7. Von Drygalski A. Curtis BR, Bougie DW, et al. Vancomycin induced thrombocytopenia. New England Journal of Medicine, 2007; 356:904-910.[antimicrobe.org]

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]
  • For others, however, the etiology may be less apparent. In these cases, drug-induced thrombocytopenia (DIT), including heparin-induced thrombocytopenia (HIT), must be a diagnostic consideration.[ncbi.nlm.nih.gov]
  • Future patient case reports should incorporate standard criteria to clearly establish the etiologic role of the drug.[ncbi.nlm.nih.gov]
  • 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]
Sex distribution
Age distribution

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]
  • 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]
  • 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]

Prevention

  • 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]
  • Prevention There is no known way to prevent hrombocytopenia. Resources Organizations American Heart Association. 7320 Greenville Ave. Dallas, TX 75231. (214) 373-6300. .[medical-dictionary.thefreedictionary.com]
  • If a medicine prevents your bone marrow from making enough platelets, the condition is called drug-induced nonimmune thrombocytopenia. Chemotherapy drugs and a seizure medicine called valproic acid may lead to this problem.[medlineplus.gov]

References

Article

  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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Last updated: 2019-06-28 09:49