Acute compartment syndrome (ACS) is defined as deterioration of the perfusion of a confined compartmental space caused by an increase in tissue pressure. Complications are frequent and could potentially be devastating following a delayed diagnosis. Fractures are the leading cause of ACS, although individuals with bleeding diathesis are at a significant risk. Most reported cases of compartment syndrome in patients with hemophilia are caused by intracompartmental bleeding following minor trauma1. We present a case of postsynovectomy compartment syndrome of the leg in a 19-year-old man with severe hemophilia A.
The patient was informed that data concerning the case would be submitted for publication, and he provided consent.
A 19-year-old male patient with a history of severe congenital hemophilia A (factor VIII <1% of normal, elevated activated partial thromboplastin time (aPTT), and other factors at normal levels) was referred to the hemophilia clinic. He complained of recurrent episodes of right knee hemarthrosis, which severely restricted his activities. He was otherwise healthy, with no relevant medical history. Except for the occasional human recombinant FVIII (rFVIII) to treat bleeding episodes, he had no notable drug history. One year before the current visit, the patient underwent radioisotope synoviorthesis using P-32, which was repeated 3 months later, according to World Federation of Hemophilia (WFH) guidelines2. The symptoms and frequency of hemarthrosis episodes were only minimally reduced. Physical examination revealed significant synovial hypertrophy of the affected knee. Anteroposterior and lateral radiographs showed satisfying joint space with minimal arthritic changes (Fig. 1). Recalcitrant hemarthrosis after radiosynovectomy in the absence of significant joint degeneration is described as an indication of surgical synovectomy2,3. The patient was scheduled for open surgical synovectomy of the right knee. The technique has been described in detail elsewhere4-6.
Preoperative hematology consult recommended testing for FVIII inhibitors, which was negative. Also, in accordance with WFH guidelines, 50 U/kg rFVIII was administered before surgery and 35 U/kg units 3 hours postoperation. Factor replacement was continued at a rate of 25 U/kg units every 8 hours2. One gram of tranexamic acid was added half an hour before surgery and every 6 hours thereafter.
The surgery was performed uneventfully, and the patient was transferred to the ward. Six hours later, he was visited complaining of severe pain in his right leg, despite receiving analgesics. Physical examination 12 hours postsurgery revealed a massive knee hemarthrosis. Palpable tenseness, severe tenderness, and impaired sensation were noted in the leg, most notably on the anterior shank. He was unable to dorsiflex the affected ankle. Distal pulses were not palpable in the right leg. An imminent compartment syndrome was suspected. The patient was immediately transferred to the operating theater. Using a pneumatic tourniquet, the previous incision was opened, and 1,000 mL of blood was evacuated from the joint. Distal pulses were palpable promptly, and perfusion to the limb was deemed adequate. Despite a vigorous factor replacement regimen, symptoms and signs of compartment syndrome recurred 5 days after the index procedure. The patient underwent a second arthrotomy, this time to evacuate 800 mL of hemarthrosis. Arterial damage was suspected, but thorough inspection revealed only diffuse oozing of blood in the joint. In accordance with the hematology consult after surgery, the patient received 10 mg prednisolone in addition to the factor replacement. The symptoms subsided, and the patient was discharged shortly thereafter. Factor replacement was continued postdischarge to achieve an FVIII level of 80 IU/dL for 2 weeks and 60 IU/dL for another 2 weeks. The dose was then tapered until suture removal. At a follow-up visit 4 weeks later, the patient was able to walk with minimal pain and near-normal range of motion and a normal neurovascular examination. Physical therapy was initiated to achieve a full range of motion. At 2-year follow-up, hemarthrosis has not recurred, and the patient has retained full knee range of motion and experiences no sensory or motor sequelae.
ACS is a surgical emergency in which circulation of the tissues is compromised following increased pressure within a compartment7. The viability of the affected tissues is threatened, and irreversible injury to muscles and nerves occurs within 6 hours8. The results of a delayed diagnosis have been fair at best, with muscle necrosis, ischemic contractures, amputation, and even death being the possible outcomes1. Early diagnosis and intervention has been found to be the most important prognostic factor by many authors1,9.
Tibial fractures are the leading cause of compartment syndrome in adults, frequently following a high-energy trauma. Other etiologies include bleeding disorders, crush injuries, and arterial injuries. The high risk of developing compartment syndrome is well recognized in patients with coagulopathy7. Absence of a history of major trauma may be misleading, as seemingly trivial traumas can lead to ACS in these patients10. Any internal or external event causing increased permeability of the capillaries, or edema of the muscular structures can lead to ACS by increasing the volume of the compartment1. Arterial occlusion causes intracellular injury, which is followed by intracompartmental edema and an increase in pressure8. We believe that in the presented case, massive intra-articular hemorrhage following synovectomy occluded the popliteal artery. Loss of peripheral pulses is a late and often ominous sign in compartment syndrome. In contrast, absence of distal pulses due to arterial occlusion is a presenting, early sign7.
ACS is a clinical diagnosis. Pain is out of proportion to the stimulus, and stretching the affected muscles will exacerbate the pain. Inappropriately severe pain is the key to diagnosis and should never be perceived as malingering. Palpable tenseness is an early and the only objective sign of an impending ACS7. Paresis may be present due to muscle involvement or an unrelated nerve injury. Paresthesia, if examined in a nonobtunded, cooperative patient, can be extremely helpful. A careful examination not only establishes a correct diagnosis but also identifies the involved compartments. In our patient, complete recovery of sensation and motor functions suggest that the pressure of a massive hemarthrosis on the neurovascular structures, rather than neural necrosis, resulted in early paresthesia and paralysis. As soon as an ACS is suspected, all circumferential wrappings should be removed down to the skin. The involved limb should be placed at the level of the heart, as higher levels have been found to deteriorate perfusion8.
With a prompt diagnosis and treatment within 12 hours of the onset of ACS, a normal limb function could be expected in 70% of the patients. A delay of more than 12 hours reduces the probability of a normal limb to 10%7. A complete, open fasciotomy is the treatment of choice in patients with a normal coagulation profile1.
Among patients with hemophilia, the incidence of compartment syndrome is unknown, with few reports in the literature1,7,11,12. The authors of the 3 largest series11,13,14 unanimously recommend replacement of the missing clotting factors as the first step, along with immobilization. An emergent fasciotomy carries the risk of uncontrollable bleeding without proper factor replacement. Fasciotomy has been reserved for the recalcitrant cases with imminent threat to the viability of the limb. We, in line with previous reports on compartment syndrome in patients with coagulation disorders, would like to emphasize that an emergent fasciotomy may not be the first step in managing an ACS in patients with hemophilia. In this case, eliminating the external pressure on the neurovascular structures, by evacuating the massive hemarthrosis, obviated the need for a fasciotomy. Pressure of the involved compartments normalized with proper factor replacement.
Corticosteroids have been used as an adjunct in the management of hemarthrosis to decrease the amount of factor administration. Since the introduction of readily available recombinant factor products, factor replacement has become the mainstay treatment of hemorrhagic episodes in patients with hemophilia. Corticosteroids are believed to increase capillary resistance and inhibit inflammatory responses. In the presented case, hemarthrosis recurred, despite a factor replacement level of 100 U/dL. Although a causative relationship cannot be established, supplementing rFVIII with oral prednisolone was successful in controlling the hemarthrosis.
As of October 2018, we were unable to find a report of imminent compartment syndrome due to hemarthrosis in hemophilia. The present case underscores clinical judgment as the main criterion for surgical treatment of compartment syndrome. Furthermore, in accordance with previous reports, we believe that fasciotomy is not the first step in the management of ACS in patients with hemophilia. Moreover, there may be a place for corticosteroids in cases of refractory hemarthrosis. Although further studies are needed to make a conclusion, addition of corticosteroids may prove to be beneficiary in cases which full dose of factors fails to contain the hemarthrosis. We would like to emphasize that surgical synovectomy is a major procedure, which requires significant tissue dissection. This would increase the risk of complications, including postoperative hemorrhage. Diligent preoperative evaluation and planning and strict adherence to the published guidelines will help prevent complications.
Note: All authors have had substantial and equal contributions to this study.
1. Donaldson J, Goddard N. Compartment syndrome in patients with haemophilia. J Orthop. 2015;12:237-41.
2. Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Ludlam CA, Mahlangu JN, Mulder K, Poon MC, Street A; Treatment Guidelines Working Group on behalf of the World Federation of Hemophilia. Guidelines for the management of hemophilia. Haemophilia. 2013;19:e1-47.
3. Rodriguez-Merchan E. Aspects of current management: orthopaedic surgery in haemophilia. Haemophilia. 2012;18:8-16.
4. Montane I, Lian E. Synovectomy of the knee for hemophilic arthropathy. J Bone Joint Surg Am. 1986;68:210-6.
5. Herring JA. Tachdjian's Pediatric Orthopaedics: From the Texas Scottish Rite Hospital for Children (Fifth edition). Philadelphia, PA: Elsevier Health Sciences; 2014.
6. Rampal V, Odent T, Torchet M, Rothschild C, Elie C, Glorion C, Padovani JP. Surgical synovectomy of the knee in young haemophiliacs: long-term results of a monocentric series of 23 patients. J Child Orthop. 2010;4:33-7.
7. Rodriguez-Merchan EC. Acute compartment syndrome in haemophilia. Blood Coagul Fibrinolysis. 2013;24:677-82.
8. Whitesides TE, Heckman MM. Acute compartment syndrome: update on diagnosis and treatment. J Am Acad Orthop Surg. 1996;4:209-18.
9. McQueen MM, Gaston P, Court-Brown CM. Acute compartment syndrome: who is at risk? J Bone Joint Surg Br. 2000;82:200-3.
10. Abdelhalim MA, Shaw CR, Al-Rub ZA, Hopper D, Hanley JP, Talks KL, Biss TT, Fearon PV. Bilateral upper limb compartment syndrome induced by strenuous exercise in a patient with haemophilia A and a low titre inhibitor. Haemophilia. 2015;21:e517-9.
11. Lancourt JE, Gilbert MS, Posner MA. Management of bleeding and associated complications of hemophilia in the hand and forearm. J Bone Joint Surg Am. 1977;59:451-60.
12. Naranja RJ Jr, Chan PS, High K, Esterhai JL Jr, Heppenstall RB. Treatment of considerations in patients with compartment syndrome and an inherited bleeding disorder. Orthopedics. 1997;20:706-9; quiz 10-1.
13. Dumontier C, Sautet A, Man M, Bennani M, Apoil A. Entrapment and compartment syndromes of the upper limb in haemophilia. J Hand Surg Br. 1994;19:427-9.
14. Lak M, Sharifian RA, Karimi K, Mansouritorghabeh H. Acquired hemophilia A: clinical features, surgery and treatment of 34 cases, and experience of using recombinant factor VIIa. Clin Appl Thromb Hemost. 2010;16:294-300.