Macroscopic haematuria: a risk factor for hypertension in haemophilia

June 2020 Science Marjolein Groot

In addition to recurrent, spontaneous bleeding, haemophilia patients also often suffer from haematuria: the presence of red blood cells in the urine. A distinction can be made between microscopic and macroscopic haematuria. With macroscopic haematuria, the urine turns pink, red or dark brown and blood clots may be present. In microscopic haematuria, the amount of blood in the urine is so small that it can only be seen under a microscope.1

It has been known for some time that adult haemophilia patients suffer from hypertension more often than the average person.2 However, the reason behind this phenomenon is not clear. It is known that genetics plays a role, in addition to one’s own behaviour – obesity, high alcohol or salt intake increases the chance of developing hypertension.3,4 Researcher dr. Qvigstad and colleagues hypothesized that it could be possible to determine another risk factor: macroscopic hematuria.5

Hypertension risk factors in haemophilia

To verify this hypothesis, 512 haemophilia patients were examined. The families and their own hypertension history were recorded. When a first-line family member had hypertension, it was noted as a ‘positive family history in hypertension’ (FH +). Blood pressure was considered high when it was above 140 mm Hg systolic, and/or diastolic above 90 mm Hg. It was also determined whether the patient had a history of macroscopic haematuria, and if so, how many episodes had occurred.

The patients were then divided into 3 groups: 1. No hypertension, 2. Hypertension with a positive family history (FH+) and 3. Hypertension and negative family history (FH-). These groups were compared using a univariate logistic regression. This showed that there was no association between the presence of macroscopic haematuria and chances of developing hypertension when there is not a first-line relative (FH-) with hypertension (Odds ratio [OR]: 0.95; 95% CI: 0.57-1.58; p = 0.84).

More hypertension with FH+ haematuria

In the haemophilia patients who did have a family history of high blood pressure (FH+), macroscopic haematuria did appear to be a risk factor. The chance of developing high blood pressure was almost 2 times (OR: 1.84; 95% CI: 1.17-2.90; p = 0.01) as high in FH+ patients with macroscopic haematuria. The risk of developing hypertension also increased with the number of episodes of macroscopic haematuria.

In addition, the known risk factors body mass index (OR: 1.18; 95% CI: 1.11-1.25; p <0.001) and age (OR: 1.08; 95% CI: 1.06 -1.11, p <0.001) emerged as significant predictors for the development of hypertension. Also diabetes (OR: 8.00; 95% CI: 3.59-17.83; p <0.001) and a low glomerular filtration rate (OR: 0.96; 95% CI: 0.95-0.97 ; p <0.001) were a risk factor as expected. Haemophilia severity did not play a significant role in the FH+ haemophilia patients (OR: 0.99; 95% CI: 0.64-1.52; p = 0.95) nor in FH- patients (OR: 0.90; 95% CI: 0.54-1.51; p = 0.70) in the chance of developing hypertension.

Prophylaxis prevents hypertension?

In general, macroscopic haematuria is considered a benign condition in haemophilia. However, this study showed that macroscopic haematuria can be a risk factor for developing hypertension, which is important because it can cause (further) renal damage, cardiovascular disease or stroke.5 Another study by the same researchers showed that frequently receiving prophylaxis reduced the incidence of macroscopic haematuria in haemophiliacs.6 Consequently, frequent prophylaxis could potentially reduce the risk of high blood pressure in haemophilia patients with a family history of hypertension.5 Further research will need to be executed to possibly demonstrate this relationship.

Sources

  1. mayoclinic.org
  2. Rosendaal FR, Briet E, Stibbe J, Herpen GV, Leuven JG, Hofman A, & Vandenbroucke JP. (1990). Haemophilia protects against ischaemic heart disease: a study of risk factors. British journal of haematology75(4), 525-530.
  3. Wang NY, Young JH, Meoni LA, Ford DE, Erlinger TP, Klag MJ. Blood pressure change and risk of hypertension associated with parental hypertension: the Johns Hopkins Precursors Study. Arch Intern Med. 2008;168(6):643‐648.
  4. Carretero OA, & Oparil S. (2000). Essential hypertension: part I: definition and etiology. Circulation101(3), 329-335.
  5. Qvigstad C, Sørensen LQ, Tait RC, de Moerloose P, Holme PA & ADVANCE Working Group. (2020). Macroscopic hematuria as a risk factor for hypertension in ageing people with hemophilia and a family history of hypertension. Medicine99(9), e19339.
  6. Qvigstad C, Tait RC, de Moerloose P, Holme PA & ADVANCE Working Group. (2020). Hematuria in aging men with hemophilia: Association with factor prophylaxis. Research and practice in thrombosis and haemostasis4(2), 309-317.
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