A practical approach to evaluating postoperative thrombocytopenia

Abstract

Identifying the cause(s) of postoperative thrombocytopenia is challenging. The postoperative period includes numerous interventions, including fluid administration and transfusion of blood products, medication use (including heparin), and increased risk of organ dysfunction and infection. Understanding normal thrombopoietin physiology and the associated expected postoperative platelet count changes is the crucial first step in evaluation. Timing of thrombocytopenia is the most important feature when differentiating causes of postoperative thrombocytopenia. Thrombocytopenia within 4 days of surgery is commonly caused by hemodilution and increased perioperative platelet consumption prior to thrombopoietin-induced platelet count recovery and transient platelet count overshoot. A much broader list of possible conditions that can cause late-onset thrombocytopenia (postoperative day 5 [POD5] or later) is generally divided into consumptive and destructive causes. The former includes common (eg, infection-associated disseminated intravascular coagulation) and rare (eg, postoperative thrombotic thrombocytopenic purpura) conditions, whereas the latter includes such entities as drug-induced immune thrombocytopenia or posttransfusion purpura. Heparin-induced thrombocytopenia is a unique entity associated with thrombosis that is typically related to intraoperative/perioperative heparin exposure, although it can develop following knee replacement surgery even in the absence of heparin exposure. Very late onset (POD10 or later) of thrombocytopenia can indicate bacterial or fungal infection. Lastly, thrombocytopenia after mechanical device implantation requires unique considerations. Understanding the timing and severity of postoperative thrombocytopenia provides a practical approach to a common and challenging consultation.

Figure 1.

Normal physiology of changes to platelet counts after surgery and the expected deviations with different pathological conditions. DITP, drug-induced immune thrombocytopenia; HIT, heparin-induced thrombocytopenia; PAT, passive alloimmune thrombocytopenia; PTP, posttransfusion purpura; TTP, thrombotic thrombocytopenic purpura. Adapted from Hoffman et al (eds) with permission.

Figure 2.

Three patients with severe early postoperative thrombocytopenia. For all 3 patients, early platelet count declines that seemed greater than expected for the clinical situation suggested occurrence of a complicating disorder. The shaded area indicates the approximate expected range of postoperative platelet counts. (A) DITP (D-ITP) of rapid onset (vancomycin). An 81-year-old woman with a recent normal platelet count underwent preoperative insertion of a radial artery catheter immediately prior to elective mitral valve replacement surgery. A hematoma unexpectedly developed at the catheter insertion site, prompting ordering of a complete blood count prior to starting CPB. The platelet count returned at 22 × 10⁹/L but cardiac surgery proceeded uneventfully, although the immediate postoperative platelet count fell further to 8 × 10⁹/L. Three platelet transfusions raised the platelet count to 73 × 10⁹/L, with subsequent decline to 5 × 10⁹/L (nadir). Hematology diagnosed DITP of rapid onset secondary to administration of preoperative antibiotic prophylaxis (both vancomycin and cefazolin were given). The patient had undergone previous remote surgery with antibiotic prophylaxis as a potential explanation of prior immune sensitization. The patient made an uneventful recovery. A blood sample tested positive for vancomycin-dependent antibodies (Abs; DITP Abs). (B) Postoperative TMA (initial presentation of congenital TTP). A 33-year-old woman was admitted posttrauma for surgery of a facial fracture. She developed unexpected progressively severe postoperative thrombocytopenia, which prompted testing for HIT Abs, which returned negative. The patient was discharged to home, without further investigations, and made a full recovery with a normal platelet count at 1-month follow-up. Three years later, the patient developed severe thrombocytopenia and morphological evidence of red cell fragments and polychromasia (per hematology technologist report of the peripheral blood smear). She was diagnosed as having congenital TTP, based upon history of recurrent thrombocytopenia and studies indicating absence ADAMTS13, lack of anti-ADAMTS13 autoantibodies, and corroborating genetic evaluation. (C) Passive alloimmune thrombocytopenia secondary to transfusion of fresh-frozen plasma containing anti–HPA-5b alloantibodies. A 52-year-old man underwent coronary artery bypass grafting using CPB. His initial postoperative course was unremarkable. However, he developed an unexpected platelet count fall to 43 × 10⁹/L, without evidence of sepsis, shock, or any other postoperative complications. As the platelet count fall occurred after he received 2 U of fresh-frozen plasma, the patient was investigated for passive alloimmune thrombocytopenia. Direct radioimmunoprecipitation of patient platelets showed IgG Abs bound to platelet GPIa/IIa. Serum obtained from the female plasma donor was subsequently shown to contain anti–HPA-5b IgG alloantibodies; the patient typed as HPA-5a/5b, and the plasma donor typed as expected as homozygous HPA-5a. Modified from Warkentin et al.