Postoperative thrombosis in patients with hemophilia and malignancy: Mechanisms and perioperative prevention and management — A scoping review

Abstract

Hemophilia is traditionally viewed as a hypocoagulable disorder, but the occurrence of postoperative venous thromboembolism (VTE) in these patients, particularly when malignancy is present, challenges this paradigm. Cancer-related and surgery-induced prothrombotic factors, when combined with perioperative factor replacement, bypassing agents, or non-factor therapies, may transiently shift the patient from a hypocoagulable state to a prothrombotic one, creating a narrow therapeutic window where both bleeding and thrombosis are clinically significant.

This review aims to synthesize the existing mechanistic and clinical evidence on postoperative thrombosis in hemophilia patients with malignancy and to identify where evidence is direct, indirect, or extrapolated. We outline a pragmatic, multidisciplinary team (MDT)-based framework for risk assessment, diagnosis, prophylaxis, and treatment, recognizing that the framework has not been validated in this rare population.

A comprehensive scoping review was conducted using MEDLINE (PubMed), Embase, Web of Science, and the Cochrane Library, covering publications from 2000 to 2025. We also hand-searched major society guidelines and consensus documents. Direct evidence addressing postoperative VTE in patients with both hemophilia and malignancy was scarce; therefore, we separated direct hemophilia perioperative evidence from indirect cancer-surgery and mechanistic evidence used for contextual interpretation.

Available hemophilia perioperative data are derived mainly from orthopedic cohorts and cannot define the incidence of postoperative VTE after cancer surgery in hemophilia. Reported thrombotic phenotypes include deep vein thrombosis (DVT), pulmonary embolism (PE), catheter-related thrombosis, and less commonly arterial events. Risk assessment should therefore integrate patient factors, cancer biology, surgical context, hemostatic treatment intensity, and FVIII/FIX peak and trough monitoring. Routine laboratory tests such as aPTT and D-dimer are frequently unreliable, supporting an imaging-first diagnostic strategy when VTE is clinically suspected.

We present a four-tier VTE risk framework as a practical organizing tool rather than a validated prediction model. Pharmacologic thromboprophylaxis or therapeutic anticoagulation may be considered only after individualized bleeding-thrombosis assessment, stable surgical hemostasis, adequate factor coverage, and continuous MDT communication from preoperative planning to post-discharge care.

Future research should focus on prospective registries, the development of standardized outcome definitions, and the validation of global coagulation assays to improve recommendations and management strategies in this evolving therapeutic landscape.