From the Guidelines
Thrombocytopenia in the context of severe infection is primarily caused by increased platelet consumption, direct pathogen-mediated platelet destruction, decreased platelet production, and immune-mediated destruction, as supported by the Surviving Sepsis Campaign guidelines 1. The mechanisms behind the onset of thrombocytopenia with severe infection are multifaceted, involving:
- Increased platelet consumption through disseminated intravascular coagulation (DIC)
- Direct pathogen-mediated platelet destruction
- Decreased platelet production in the bone marrow due to inflammatory cytokines
- Sequestration of platelets in the enlarged spleen (hypersplenism)
- Immune-mediated destruction through antibodies targeting platelets According to the guidelines, in patients with severe sepsis, prophylactic platelet transfusion is suggested when counts are < 10,000/mm3 (10 × 109/L) in the absence of apparent bleeding, and when counts are < 20,000/mm3 (20 × 109/L) if the patient has a significant risk of bleeding 1. Key considerations for managing thrombocytopenia in severe infection include:
- Monitoring platelet counts closely
- Administering platelets prophylactically based on the guidelines
- Avoiding medications that may exacerbate thrombocytopenia
- Providing supportive care for patients with significant bleeding or very low platelet counts.
From the Research
Causes of Onset of Thrombocytopenia with Severe Infection
- Infections with protozoa, bacteria, and viruses can cause thrombocytopenia with or without disseminated intravascular coagulation 2
- Common infections that present as fever with thrombocytopenia include dengue, malaria, scrub typhus, and other rickettsial infections, meningococci, leptospira, and certain viral infections 2
- Thrombocytopenia in bacterial infections can occur as a part of sepsis with disseminated intravascular coagulation 2
- Patients with sepsis may also develop hemophagocytic histiocytosis with phagocytosis of platelets and leucocytes in the bone marrow histiocytes 2
- Both Gram-positive and Gram-negative bacterial infections can lead to sepsis 2
- Elevated platelet-associated IgG has been implicated in thrombocytopenia 2
- Platelets tend to adhere to damaged vascular surfaces in meningococcemia 2
Medication-Induced Thrombocytopenia
- Piperacillin-tazobactam (TZP) is a known culprit of rapid and severe onset thrombocytopenia, especially in critically ill or immunocompromised patients 3, 4
- Thrombocytopenia can occur even without previous exposure to the medication 3
- TZP-induced thrombocytopenia can resolve within three days of withdrawal 3
- Platelet dysfunction is a little-known mechanism of TZP-induced bleeding, which can be detected only by platelet functional tests 5
Evaluation and Management
- Thrombocytopenia is a commonly encountered hematologic problem in inpatient and ambulatory medicine 6
- The many underlying mechanisms of thrombocytopenia include pseudothrombocytopenia, splenic sequestration, and marrow underproduction and destruction 6
- A framework for evaluation and brief descriptions of management can be presented in a case-based format 6