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You Make the Call: What prophylactic treatment would you recommend for a basketball player who has had multiple episodes of hematoma?

February 23, 2024

March 2024

Bethany T. Samuelson Bannow, MD, MCRBethany T. Samuelson Bannow, MD, MCR
Assistant Professor of Medicine
Oregon Health & Science University

 

 


CLINICAL DILEMMA

I was referred an 18-year-old collegiate basketball player who has had three episodes of right thigh hematoma after trauma, the first of which occurred in 2020. He then had two repeat injuries in 2023 after receiving a knee to the thigh. He has a prolonged partial thromboplastin time. His factor VIII and IX levels are normal, and factor XI is 43%. He has no family history of bleeding disorders and wants to return to play. Is it reasonable to recommend prophylactic fresh frozen plasma prior to games, or is treatment with injury only recommended? Would prophylactic recombinant factor VIIa or tranexamic acid be appropriate treatment options? Should this patient be precluded from play?


EXPERT OPINION

This patient has three findings that may or may not be related: an abnormal bleeding history, a prolonged partial throm­boplastin time (PTT), and a mildly decreased factor XI (FXI) level. In practice, identification of abnormal bleeding via history and physical is always the first step. This patient’s history of three episodes of trauma-induced hematoma is clearly abnormal. Laboratory workup may aid in identifying specific deficiencies but should not stand alone without a bleeding history.

This patient has an isolated prolonged PTT, the differential for which includes deficiencies of factor VIII (FVIII), factor IX (FIX), or FXI; anticoagulant exposure; factor XII deficiency; prekallikrein or high-molecular-weight kininogen; or lupus anticoagulant. In a patient with bleeding and without exposure to anticoagulants, deficiencies of FVIII, FIX, and FXI rise to the top of this list. However, sensitivity of PTT assays varies widely, and some assays will not even prolong in the presence of factor levels as low as 30%. The upper limit of detection of decreased FXI levels by commonly used PTT assays ranges from 38 to 52 U/dL, and only one of five assays would prolong in the setting of a level of 43 U/dL.1 Although this patient’s prolonged PTT may be the result of FXI deficiency, repeating testing to rule out lab errors and mixing studies to detect potential inhibitors will be essential.

The next question to ask is whether an FXI level of 43% is adequately explanatory of this patient’s bleeding history. While often referred to as “hemophilia C,” FXI deficiency presents quite differently from hemophilia A and B. Common features include bleeding in areas with high fibrinolytic activity, surgery-associated bleeding, and a lack of correlation between symptoms and FXI activity. As the phenotype of any FXI deficiency is typically mild and hematomas or intramuscular bleeding represent an atypical presentation, alternative explanations such as the presence of an anatomic anomaly or neoplasm must be considered.2,3 I also always ask about hypermobility because Ehlers-Danlos syndrome is frequently associated with excessive bleeding, including muscle hematomas.4

This brings us to the question about prophylaxis for future bleeding events in this athlete. In the U.S., the most common treatment options for FXI deficiency include fresh frozen plasma (FFP) and antifibrinolytics such as tranexamic acid (TXA). FXI concentrate, while available in some parts of the world, is not available in the U.S. Successful use of low-dose recombinant FVIIa for surgical prophylaxis has also been described in patients with FXI inhibitors.5

Guidance around prophylaxis in athletes with FXI deficiency is lacking, and guidance provided for patients with other types of hemophilia requires significant interpretation, suggesting that basketball can be associated with a low-moderate, moderate, or moderate-high risk level for bleeding. Based on the level at which this athlete plays and his history, we will consider him to be at the moderate-high risk level, in which prophylaxis is advisable.

FFP is rarely a convenient or practical therapy, even in the perioperative setting, and for procedures, such as epidural analgesia and cesarean delivery, replacement is typically only recommended for those with FXI levels less than 40 U/dL and a bleeding history.6 Recombinant FVIIa is likely to be effective but has a short half-life, requires intravenous administration, and is associated with an increased risk of thrombosis. However, the benefits of TXA in such situations are potentially significant, given that it is orally administered, targets the process of fibrinolysis — which seems to have a link with FXI deficiency-associated bleeding — and is generally well tolerated. Additionally, TXA has demonstrated efficacy and utility in a wide variety of bleeding disorders and is beneficial in patients with connective tissue disorder-associated bleeding. As a result, I would favor the use of TXA as prophylaxis prior to practice and games in this athlete.

References

  1. Toulon P, Eloit Y, Smahi M, et al. In vitro sensitivity of different activated partial thromboplastin time reagents to mild clotting factor deficiencies. Int J Lab Hematol. 2016;38(4):389-396.
  2. Shu AL, Iwema JR, Browning S., et al. Recurrent intramuscular hematoma as a presentation of pleomorphic sarcoma. ACS Case Reviews in Surgery. 2019;2(4).
  3. Sakamoto A, Okamoto T, Matsuda S. Chronic expanding hematoma in the extremities: a clinical problem of adhesion to the surrounding tissues. BioMed Res Intl. 2017;2017:4634350.
  4. Kumskova M, Flora GD, Staber J, et al. Characterization of bleeding symptoms in Ehlers-Danlos syndrome. J Thromb Hemost. 2023;21(7):1824-1830.
  5. Salomon O, Zivelin A, Livnat T, et al. Inhibitors to factor XI in patients with severe factor XI deficiency. Semin Hematol. 2006;43(1 Suppl 1):S10-12.
  6. Gerber GF, Klute KA, Chapin J, et al. Peri- and postpartum management of patients with factor XI deficiency. ClinAppl Thromb Hemost. 2019;25:10.1177/1076029619880262.

NEXT MONTH'S CLINICAL DILEMMA

I have a 20-year-old female patient with acute promyelocytic leukemia (APL). She had an unusual presentation with a right clavicular mass that had been growing very slowly for one year and intermittent symptoms of sciatica. Her blood counts and coagulation labs were normal. Initially, her diagnosis was consistent with an Ewing sarcoma, but a biopsy of the clavicular mass showed APL with t(15;17) and trisomy 8 (confirmed by fluorescence in situ hybridization [FISH] and positive for PML-RARA by reverse transcription polymerase chain reaction [RT-PCR]). A PET scan only showed avidity in the clavicular mass and sacrum, and an MRI of the brain and spine showed soft tissue expansion of the sacrum into the spinal canal (extradural) that was causing the sciatica. A posterior iliac crest bone marrow biopsy had normal morphology, karyotype, and FISH results for t(15;17), but was positive for PML-RARA by RT-PCR.

She was started on induction therapy with the APML4 regimen of all-trans-retinoic acid (ATRA), idarubicin, and intravenous arsenic trioxide (IV ATO; ATRA 45 mg/m2 daily plus idarubicin 12 mg/m2 on days 2, 4, 6, and 8, followed with IV ATO 0.15 mg/kg daily starting on day 9). She has tolerated this regimen well with no differentiation syndrome.

She also had screening lumbar puncture with concurrent intrathecal chemotherapy (50 mg of cytarabine) to check for central nervous system (CNS) involvement. The spinal fluid analysis showed a white cell count of 17 x 106/L, red blood cell count of 4 x 106/L, and morphology of cells that was concerning for promyelocytes. Based on these results, I believe she has CNS involvement.

Before knowing about the CNS disease, I planned to use APML4 induction, followed by four cycles of ATRA plus ATO consolidation (as per the APML4 ALLG trial), but no maintenance. Now, in light of the CNS disease, how should I treat her?

How would you respond? Email us at ashclinicalnews@hematology.org.


Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.

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