Haemophilia, bleeding and bubbles

Inspired by Oliveira et al 2020,[1] and Ma et al 2020.[2]

OA – osteoarthritis

WFH – World Federation of Hemophilia (that’s how they spell it)

TENS – transcutaneous electrical nerve stimulation

ASD – atrial septal defect

key to acronyms

This blog follows on in a way from our consideration of OA last time. The subject is chronic pain in haemophilia, and the pain principally derives from joint disease secondary to intra-articular bleeding.

I will start with some background and stats from the WFH Guidelines 2012 (direct copy with correction of English from American to British).[3]

Haemophilia is an X-linked congenital bleeding disorder caused by a deficiency of coagulation factor VIII (FVIII) (in haemophilia A) or factor IX (FIX) (in haemophilia B). The deficiency is the result of mutations of the respective clotting factor genes.

Haemophilia has an estimated frequency of approximately one in 10 000 births.

Estimations based on the WFH’s annual global surveys indicate that the number of people with haemophilia in the world is approximately 400 000.[4]

WFH guideline 2012 [3]

Me again, just butting in here in the middle of the quote: I cannot see where they get the figure 400 000. The figure is not to be found in their reference (Stonebraker 2010). But good old Stonebraker (great name) has a more contemporary paper with a figure of just over 220 000 for haemophilia A and B, and just over 350 000 for all bleeding disorders in 2018.[5]

Haemophilia A is more common than haemophilia B, representing 80–85% of the total haemophilia population.

Haemophilia generally affects males on the maternal side. However, both F8 and F9 genes are prone to new mutations, and as many as 1/3 of all cases are the result of spontaneous mutation where there is no prior family history.

WFH guideline 2012 [3]

1/3 of all cases are the result of spontaneous mutation

Now that last bit about spontaneous mutation was interesting and a bit worrying.

Oliveira et al have performed a neat randomised controlled trial (n=28) of 5 sessions of acupuncture versus the same number of electrotherapy sessions with TENS. They describe it as single blind…

Acupuncture was superior to TENS in most, but not all outcomes, and appeared to provide greater satisfaction.

This is all very well, but ideally we prevent the joint deterioration in the first place, and that can be done in a number of ways now, but originally it was demonstrated in boys with haemophilia A using regular FVIII infusions.[6] Subsequently a number of different strategies have proved successful,[7] including a variety of monoclonal antibodies.

In summary, it is not surprising to find that acupuncture may improve symptoms in this degenerative joint disease, but the future is surely in some form of gene therapy to normalise haemostasis, and thus prevent this form of joint disease in the first place.

Whilst on the subject of bleeding I thought it was a good time to include the following adverse event report associated with acupuncture treatment.[2] It is no surprise that acupuncture can occasionally cause significant bleeding, and in this case the haematoma contained just over 100ml of blood, which would create a very noticeable bump, if it wasn’t tucked away somewhere inside one of your bingo wings. For those of you not familiar with the British pastime known as bingo, often favoured by more elderly persons, the aforementioned wings refer to folds of skin and subcutaneous fat that hang from the upper arms and become agitated when you raise your hands and excitedly scream ‘house’ – an indication that you may have won that particular game of bingo.

ultrasound imaging of microbubbles

The notable aspect of this report was that ultrasound imaging of microbubbles entering the haematoma was used to demonstrate active bleeding, and this led to treatment with compression bandaging.

This is the first time I have seen microbubbles used in an acupuncture case report, and it reminds me of a similar investigation I observed many years ago in Plymouth, when commercial divers who had suffered decompression sickness were being assessed for ASDs by injecting microbubbles intravenously whilst simultaneously performing echocardiography (ultrasound of the heart). I was the one injecting the microbubbles, which in itself seems a bit risky, and I was impressed and alarmed at how quickly they could be seen in the chambers of the right side of the heart. We then looked carefully to see if any wisp of bubbles crossed to the left. That was the only time I injected bubbles into someone’s veins.

Reference list

1         Oliveira KCP, Ricciardi JB da S, Grillo CM, et al. Acupuncture as a therapeutic resource for treatment of chronic pain in people with haemophilia. Haemophilia 2020;:hae.14151. doi:10.1111/hae.14151

2         Ma J-J, Zhang B. Diagnosis of an actively bleeding brachial artery hematoma by contrast-enhanced ultrasound: A case report. World J Clin Cases 2020;8:3835–40. doi:10.12998/wjcc.v8.i17.3835

3         Makris M, Kasper C. The World Federation of Hemophilia guideline on management of haemophilia. Haemophilia 2013;19:1. doi:10.1111/hae.12074

4         Stonebraker JS, Bolton-Maggs PHB, Soucie JM, et al. A study of variations in the reported haemophilia A prevalence around the world. Haemophilia 2010;16:20–32. doi:10.1111/j.1365-2516.2009.02127.x

5         Stonebraker JS, Bolton-Maggs PHB, Brooker M, et al. The World Federation of Hemophilia Annual Global Survey 1999-2018. Haemophilia 2020;26:591–600. doi:10.1111/hae.14012

6         Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus Episodic Treatment to Prevent Joint Disease in Boys with Severe Hemophilia. N Engl J Med 2007;357:535–44. doi:10.1056/NEJMoa067659

7         Mahlangu JN, Blanchette V, Klamroth R. Redefining prophylaxis in the modern era. Haemophilia 2020;:hae.14035. doi:10.1111/hae.14035

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Declaration of interests MC