European Journal of Cardiovascular Medicine

Hemophilia A is an X-linked recessive bleeding disorder caused by deficiency of coagulation factor VIII and affects approximately 1 in 5,000 male births globally (1). Although advances in factor replacement and prophylactic regimens have significantly improved survival and quality of life, musculoskeletal bleeds remain a dominant cause of morbidity (2,3). Deep muscle hemorrhages, including those involving the iliopsoas and gluteal regions, can present with substantial bleeding and may lead to neurovascular compromise, pseudotumor formation, and compartment syndromes (3–5).

Intramuscular injections constitute a well-recognized, yet preventable, iatrogenic cause of muscle hemorrhage in hemophilia. Despite strong recommendations from the World Federation of Hemophilia (WFH) to avoid intramuscular administration whenever feasible (6, 7), injection-related hematomas continue to occur—especially in peripheral healthcare settings where hemophilia status may not be disclosed or expertise is limited. World Federation of Hemophilia  recommends that children and adults with hemophilia should follow the same routine immunization schedule as the general population. However, whenever possible, vaccines should be administered subcutaneously rather than by the intramuscular or intradermal route. Subcutaneous vaccination is considered safe and effective and usually does not require prophylactic clotting factor infusion. If an intramuscular injection is unavoidable, a dose of clotting factor concentrate should be provided beforehand. The smallest appropriate needle (25–27 gauge) should be selected, an ice pack may be applied to the intended site for a few minutes prior to injection, and firm pressure should be maintained at the site for at least 10 minutes afterwards to minimize bleeding and swelling (6).

Although isolated case reports describe spontaneous and traumatic hematomas, comprehensive documentation of post-injection bleeds with superimposed infection and extensive anatomical spread is limited in the literature (7, 8).

The rationale of this case report is to highlight the ongoing risk posed by intramuscular injections in adult patients with severe hemophilia, demonstrate the complexities of managing massive infected deep muscle hematomas, and reinforce contemporary evidence-based strategies for hemostasis, infection control, and interventional drainage.

This report additionally aims to contextualize the patient’s clinical course with existing literature to better inform preventive strategies and management protocols.

A 35-year-old man with severe Hemophilia A presented with a two-week history of progressive left gluteal swelling and severe pain following administration of an intramuscular tetanus toxoid injection. The patient had not disclosed his bleeding disorder at the time of vaccination. At presentation, he was afebrile but unable to lie supine because of a large, warm, and tender swelling extending from the gluteal region to the popliteal fossa.

Initial laboratory evaluation showed hemoglobin 10.9 g/dL, leukocytosis (19,150/mm³), platelet count 1.5 × 10⁵/mm³, and CRP 362 mg/L. Liver and renal function tests were normal. Inhibitor screen was negative. Ultrasound revealed a 17 × 8.6 × 5.1 cm intramuscular collection with internal echoes. Empirical antibiotics—piperacillin–tazobactam, linezolid, and metronidazole—were initiated, and factor VIII replacement commenced to maintain trough levels above 30%.

On day two, hemoglobin dropped to 8.9 g/dL, necessitating transfusion. Despite continued factor support, swelling persisted and CRP rebounded (254 → 373 mg/L), raising concern for infection. Repeat ultrasound revealed persistent hematoma with a new left psoas collection. Antibiotics were escalated to meropenem with continuation of linezolid and metronidazole.

Thrombocytopenia (75,000/mm³) subsequently developed, attributed to linezolid-induced hematotoxicity (1), prompting its discontinuation. Vancomycin was substituted. CT angiography later demonstrated a massive multiloculated collection measuring 46.5 × 14.7 × 6 cm with air pockets, but no contrast extravasation. Total factor usage reached approximately 134,000 IU.

A multidisciplinary team comprising internal medicine, surgery, orthopedics, plastic surgery, and interventional radiology recommended image-guided drainage under factor coverage. Approximately 1,200 mL of altered blood was aspirated. Post-procedure, factor VIII levels were maintained above 50% for 48 hours, then above 30% for 5 days before tapering. Swelling regressed, CRP declined to 40 mg/L, and inhibitor screens remained negative. The patient was discharged with an advice of emicizumab for secondary prophylaxis.

Table 1- Key Laboratory and Imaging Findings

This case highlights a rare yet clinically significant consequence of intramuscular injection in severe Hemophilia A: extensive, multiloculated gluteal and thigh hematoma progressing to secondary infection. While deep muscle bleeds are well documented in hemophilia, cases of massive, infected post-injection hematomas extending across multiple muscle compartments are infrequently reported (3,7,8).

Hematoma formation and anatomical spread: Deep muscle bleeds, particularly those in the gluteal and iliopsoas regions, can dissect extensively along fascial planes because of large muscle mass and rich vascular supply (3,9 ). The progressive extension of the hematoma in this patient—from gluteal to posterior thigh and subsequently psoas—aligns with anatomical patterns described in musculoskeletal imaging studies (9, 10).

Infection in deep muscle hematomas: Secondary infection is uncommon but poses significant diagnostic and therapeutic challenges. Ramanan et al. describe infected intramuscular hematomas as a rare entity in hemophilia but associated with substantial morbidity (8). In the present case, early elevation and rebound of CRP, air pockets on CT, and persistent swelling guided timely escalation of antibiotics and drainage.

Linezolid-induced thrombocytopenia: The development of thrombocytopenia following prolonged linezolid therapy is consistent with hematologic toxicity reported by Gerson et al. The prompt recovery after drug withdrawal in this case mirrors observations in previous studies (11).

Factor replacement needs: WFH guidelines recommend maintaining FVIII levels above 50% for major muscle bleeds for 7–10 days (6). In our patient, total FVIII usage exceeded 130,000 IU, comparable to doses reported in severe deep muscle bleeds requiring interventional management (3, 12, 13). The persistently negative inhibitor screens facilitated effective hemostatic response.

Role of Imaging and Interventional Management:Serial imaging enabled timely recognition of hematoma expansion and superinfection, consistent with findings from El-Assal et al. on the importance of multimodality imaging for monitoring muscle bleeds (4,13). Minimally invasive drainage, now favored over open surgery, significantly reduces bleeding risk and recovery time (4,12,14).

Rationale and Uniqueness of the Case

This report is clinically significant for several reasons:

1. Massive anatomical extent: A 46.5 cm multiloculated infected hematoma across gluteal, thigh, and psoas compartments is rarely documented.
2. Injection-related precipitant: Despite standardized guidelines, iatrogenic intramuscular injections remain a preventable cause of morbidity in hemophilia.
3. Complexity of management: The case required large-volume factor support, broad-spectrum antibiotics, thrombocytopenia management, and image-guided drainage.
4. Implications for health systems: This case underscores the need for stringent vaccination guidelines and awareness among peripheral healthcare providers.

Limitations

As a single case report, generalizability is limited. Microbiological cultures were not reported, which could have provided etiological clarification. Long-term functional outcomes and the patient's adherence to emicizumab prophylaxis could not be fully assessed.

Key Highlights

• Injection-related hematomas, although rare today, continue to occur due to gaps in awareness.
• Serial imaging is essential for tracking bleed progression and detecting infection.
• Management requires rigorous hemostatic therapy, vigilance for drug toxicity, and multidisciplinary decision-making.

Early drainage under factor coverage is effective for large, infected hematomas

This case underscores the potentially catastrophic consequences of intramuscular injections in patients with severe hemophilia. The extensive hematoma formation, secondary infection, and need for prolonged multidisciplinary care highlight the importance of adherence to established vaccination guidelines, proactive patient education, and avoidance of intramuscular routes.

Successful patient outcomes depend on timely imaging, adequate and sustained factor replacement, inhibitor surveillance, and appropriate interventional procedures. While deep muscle hematomas remain a known complication in hemophilia, this case emphasizes that even a single avoidable intramuscular injection can result in significant morbidity.

Strengthening immunization protocols, improving awareness among frontline healthcare providers, and ensuring availability of prophylaxis remain fundamental to preventing such complications. Further research and pooled analyses are needed to guide optimal management of infected and extensive intramuscular hematomas in hemophilia.

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