Investigators discovered that mechanical (P <.001) and pressure (P <.05) pain thresholds were significantly reduced over a period of 1 year in patients with hemophilia, compared to a healthy control group. Pain sensitivity to mechanical stimuli increased significantly in the knee joints of the patients, compared to controls (P =.028). Mechanical detection thresholds increased significantly at all sites evaluated (P <.01).

The authors remarked, “Mechanical hyperalgesia could be demonstrated for ankle joints based on the statistically significant differences in pressure [pain threshold] and mechanical pain sensitivity between PwH and controls.” They detected secondary hyperalgesia at the hand joints of patients with hemophilia, suggesting that “not only peripheral sensitization, but also sensitization of the central pain-processing system can be found in [patients with hemophilia].”

Subsequently, the authors recommend that “the primary goal of early tailored (pain) management should also be to prevent pathophysiological changes at peripheral and central levels” for patients with hemophilia. They emphasize the importance of identification of pain conditions as early as possible, as well as assessment of the efficacy of hematological therapies.

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Study Methods

The investigators evaluated 24 adult patients with hemophilia and 21 age-matched healthy controls twice. Of the 24 PwH, 19 patients had severe hemophilia A and 3 had severe hemophilia B; all patients with severe hemophilia received prophylactic treatment with standard half-life therapy products.

Baseline measurements utilized Quantitative Sensory Testing (QST) to examine 21 knee joints, 61 ankle joints, and 45 dominant hands for detection and pain thresholds. The QST assessed thermal, mechanical, and vibration detection thresholds and thermal, mechanical, and pressure pain thresholds.

The locations of assessments included the medial joint space of the knee and the lateral joint space of the ankle for affected sites, as these lower extremity joints experience more arthropathies due to repeated joint bleeds in patients with hemophilia. Investigators evaluated the contralateral knee and ankle joints as well as the thenar eminence of the dominant hand as reference points. After 1 year, the researchers repeated these measurements to assess the changes over time.

Study Limitations

The limitations of this study included the short time period of 1 year, lack of sensitivity of the QST to detect minute changes in the somatosensory profile, and effects of the natural aging process on the results. Another limitation in some cases was the possibility of human immunodeficiency virus (HIV)-induced neuropathy impacting the results.

The authors speculated that future studies should analyze data in the context of the severity and number of joint bleeding episodes for patients with hemophilia.


Krüger S, Herzig M, Hilberg T. Changes in pain profile of patients with haemophilia during 1-year follow-up. Haemophilia. Published online August 13, 2021. doi:10.1111/hae.14380