#pseudohemophilia

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[storyswept]

Troubled Blood: Genetics Strike Again

After Lethal White and its mention of lethal white syndrome, a genetic disorder which affects horses, followed Troubled Blood which, guess what, also features a genetic disorder, this one related to bleeding.

‘Have you met Roy? Margot’s husband?’ (...) He’s a haemophiliac, isn’t he?’ asked Gupta. ‘Not that I’ve heard,’ said Strike, surprised. ‘Yes, yes,’ said Gupta ‘I think so, I think he is. He was a haematologist by profession, and his mother told me that he had chosen the specialty because of his own condition.

- Troubled Blood, Chapter 10

We learn in the same conversation that Roy had been ruled out early on as a suspect in Margot's disappeareance, but not the reason why:

‘Now, that was a curious thing. Inspector Talbot told me at the start of my own police interview that Roy had been completely ruled out of their enquiries – which I’ve always thought was an odd thing to tell me. Don’t you find it so? This was barely a week after Margot’s disappearance. (...)'

- Troubled Blood, Chapter 10

While Dr. Gupta believes him to be a haemophiliac, we later learn that Roy Phipps is actually afflicted with a severe form of von Willebrand disease and that he couldn't have left the house at the time of Margot's diseapperance, being bedridden after a serious bleed.

her husband, Dr Roy Phipps, who suffers from von Willebrand Disease, was ill at home and confined to bed at the marital home in Ham on the 11th October. ‘Following several inaccurate and irresponsible press reports, we would like to state clearly that we are satisfied that Dr Roy Phipps had nothing to do with his wife’s disappearance,’ DI Bill Talbot, the detective in charge of the investigation, told newsmen. ‘His own doctors have confirmed that walking and driving would both have been beyond Dr Phipps on the day in question and both Dr Phipps’ nanny and his cleaner have given sworn statements confirming that Dr Phipps did not leave the house on the day of his wife’s disappearance.’

‘What’s von Willebrand Disease?’ asked Robin. ‘A bleeding disorder. I looked it up. You don’t clot properly. Gupta remembered that wrong; he thought Roy was a haemophiliac. ‘There are three kinds of von Willebrand Disease,’ said Strike. ‘Type One just means you’d take a bit longer than normal to clot, but it shouldn’t leave you bedbound, or unable to drive. I’m assuming Roy Phipps is Type Three, which can be as serious as haemophilia, and could lay him up for a while. But we’ll need to check that.

- Troubled Blood, Chapter 14

As Dr Phipps was bedbound due to his recent accident—” ’ ‘Anna told you about Roy’s von Willebrand Disease?’ said Cynthia anxiously. ‘Er – I don’t think she told us, but it’s mentioned in the police report.’ ‘Oh, didn’t she say?’ said Cynthia, who seemed unhappy to hear it. ‘Well, he’s a Type Three. That’s serious, as bad as haemophilia. His knee swelled up and he was in a lot of pain, could hardly move,’ said Cynthia. ‘Yes,’ said Strike, ‘it’s all in the police—’ ‘No, because he’d had an accident on the seventh,’ said Cynthia, who seemed determined to say this. ‘It was a wet day, pouring with rain, you can check that. He was walking around a corner of the hospital, heading for the car park, and an out-patient rode right into him on a pushbike. Roy got tangled up in the front wheel, slipped, hit his knee and had a major bleed. These days he has prophylactic injections so it doesn’t happen the way it used to, but back then, if he injured himself, it could lay him up for weeks.’

- Troubled Blood, Chapter 35

Dr Gupta's mistake might be a historical nod to this disease's original name, “hereditary pseudohemophilia”. First described by Dr Erik von Willebrand in 1926, the clinical presentation of von Willebrand disease differs from haemophilia's in two major ways:

different genetic transmission: whereas von Willebrand disease is a autosomal genetic disorder, haemophilia is a X-linked genetic disorder. This means that the likelihood of having von Willebrand disease isn't influenced by one's sex, unlike in haemophilia which manifests mostly in males (as they only inherit one X chromosome).

different bleeding pattern: while haemophilia is characterised by deep subcutaneous or joint bleeding, von Willebrand disease mostly presents in the form of mucocutaneous bleeding (e.g. easy bruising, nosebleeds, gum bleeding, heavy menstrual bleeding, excessive bleeding after operations or trauma...) However, some forms of von Willebrand disease (such as type 3, the particular form of von Willebrand disease that Roy Phipps has) can cause haemophilia-like bleeding, in this case resulting in a swollen knee.

Von Willebrand's disease is the most frequent genetic bleeding disorder, estimated to occur in 0.1% to 1% of the population. Nowadays, we know that this disease is caused by a deficency or defect of a particular plasma protein, known as von Willebrand factor. As mentioned in Troubled Blood, von Willebrand disease is currently classified in 3 types:

Type 1, a partial deficiency of von Willebrand Factor, is generally the mildest form of the disease.

Type 2 results from qualitative defects of the von Willebrand Factor.

Type 3, a complete deficiency of von Willebrand Factor, presents as severe bleeding. Because the deficiency is complete, it doesn't respond to treatment with desmopressin. Desmopressin, which increases the release of von Willebrand factor in the bloodstream, was first used to prevent bleeding during interventions on von Willebrand disease patients in 1977. This discovery would have had little impact on Dr. Phipps' life who would have had to continue to rely on plasma derivates. Lately, recombinant von Willebrand factor has become a therapeutic option.

Interestingly, though it's kind of logical when you think about it, consanguinity increases the odds of having type 3. Are we to understand that Roy wasn't the only one to marry a relative in the family? I do wonder what caused Galbraith/Rowling to afflict Margot's husband (who would normally be the number one suspect) with this particular disease. Was it merely to create a parallel between "Lethal White" and "Troubled Blood" or did she wish to raise awareness for the disease? I don't think I have read a novel so far where this disease is mentioned by name, have you? Further reading / Sources:

Swami A., Kaur V. von Willebrand Disease: A Concise Review and Update for the Practicing Physician. Clinical and Applied Thrombosis/Hemostasis. 2016;23(8):900-910. doi:10.1177/1076029616675969

Favaloro E. Rare forms of von Willebrand disease. Annals of Translational Medicine. 2018;6(17):345-345.  doi: 10.21037/atm.2018.09.10. PMID: 30306084; PMCID: PMC6174185.

Mannucci P. Desmopressin: an historical introduction. Haemophilia. 2007;14:1-4. doi:10.1111/j.1365-2516.2007.01609.x

Keeney S. Recombinant VWF: is this the answer for treatment of von Willebrand disease?. Clinical Investigation. 2012;2(8):755-757. doi:10.4155/cli.12.79

[klexasorianoposts-blog]

History of Hemophilia

Incidences of excessive or abnormal bleeding were first recorded hundreds of years ago. The Talmud, a collection of Jewish rabbinical writings on laws and traditions, from the 2nd century AD, stated that baby boys did not have to be circumcised if two of their brothers had previously died from the procedure. The New Testament of the Bible mentioned a woman who had hemorrhaged for 12 years, before touching the hem of Jesus’ garment, when she was healed. Abulcasis, or Abu Khasim, a 10th century Arabian physician, described families whose male relatives died from uncontrolled bleeding after trauma.

In 1803, John Conrad Otto, a Philadelphia physician, was the first to publish an article recognizing that a hemorrhagic bleeding disorder primarily affected men, and ran in certain families. He traced the disease back to a female ancestor living in Plymouth, New Hampshire, in 1720. Otto called the males “bleeders.” In 1813, John Hay published a paper in the New England Journal of Medicineproposing that affected men could pass the trait for a bleeding disorder to their unaffected daughters. Then in 1828, Friedrich Hopff, a student at the University of Zurich, and his professor Dr. Schonlein, are credited with coining the term “haemorrhaphilia” for the condition, later shorted to “haemophilia.”

In 1926 Finnish physician Erik von Willebrand published a paper describing what he called “pseudohemophilia,” a bleeding disorder affecting men and women equally. It was later named von Willebrand disease. In 1957 Inga Marie Nilsson and researchers at the Malmo University Hospital in Sweden determined that VWD was caused by low levels or deficient von Willebrand factor.

In 1947, Dr. Alfredo Pavlovsky, a doctor in Buenos Aires, Argentina, distinguished two types of hemophilia in his lab—A and B.

Factor I deficiency was first described in 1920. Factors II and V deficiency were identified in the 1940s. The 1950s saw an explosion of work on rare factor deficiencies, as deficiencies of FVII, X, XI and XII were first recognized. In 1960, FXIII deficiency was described.

Source: https://www.hemophilia.org/Bleeding-Disorders/History-of-Bleeding-Disorders

[klexaaaa-blog]

History of Hemophilia

Incidences of excessive or abnormal bleeding were first recorded hundreds of years ago. The Talmud, a collection of Jewish rabbinical writings on laws and traditions, from the 2nd century AD, stated that baby boys did not have to be circumcised if two of their brothers had previously died from the procedure. The New Testament of the Bible mentioned a woman who had hemorrhaged for 12 years, before touching the hem of Jesus’ garment, when she was healed. Abulcasis, or Abu Khasim, a 10th century Arabian physician, described families whose male relatives died from uncontrolled bleeding after trauma.

In 1803, John Conrad Otto, a Philadelphia physician, was the first to publish an article recognizing that a hemorrhagic bleeding disorder primarily affected men, and ran in certain families. He traced the disease back to a female ancestor living in Plymouth, New Hampshire, in 1720. Otto called the males “bleeders.” In 1813, John Hay published a paper in the New England Journal of Medicineproposing that affected men could pass the trait for a bleeding disorder to their unaffected daughters. Then in 1828, Friedrich Hopff, a student at the University of Zurich, and his professor Dr. Schonlein, are credited with coining the term “haemorrhaphilia” for the condition, later shorted to “haemophilia.”

In 1926 Finnish physician Erik von Willebrand published a paper describing what he called “pseudohemophilia,” a bleeding disorder affecting men and women equally. It was later named von Willebrand disease. In 1957 Inga Marie Nilsson and researchers at the Malmo University Hospital in Sweden determined that VWD was caused by low levels or deficient von Willebrand factor.

In 1947, Dr. Alfredo Pavlovsky, a doctor in Buenos Aires, Argentina, distinguished two types of hemophilia in his lab—A and B.

Factor I deficiency was first described in 1920. Factors II and V deficiency were identified in the 1940s. The 1950s saw an explosion of work on rare factor deficiencies, as deficiencies of FVII, X, XI and XII were first recognized. In 1960, FXIII deficiency was described.

Source: https://www.hemophilia.org/Bleeding-Disorders/History-of-Bleeding-Disorders

[hemophiliadisorder]

History Of Hemophilia

Incidences of excessive or abnormal bleeding were first recorded hundreds of years ago. The Talmud, a collection of Jewish rabbinical writings on laws and traditions, from the 2nd century AD, stated that baby boys did not have to be circumcised if two of their brothers had previously died from the procedure. The New Testament of the Bible mentioned a woman who had hemorrhaged for 12 years, before touching the hem of Jesus’ garment, when she was healed. Abulcasis, or Abu Khasim, a 10th century Arabian physician, described families whose male relatives died from uncontrolled bleeding after trauma.

In 1803, John Conrad Otto, a Philadelphia physician, was the first to publish an article recognizing that a hemorrhagic bleeding disorder primarily affected men, and ran in certain families. He traced the disease back to a female ancestor living in Plymouth, New Hampshire, in 1720. Otto called the males “bleeders.” In 1813, John Hay published a paper in the New England Journal of Medicineproposing that affected men could pass the trait for a bleeding disorder to their unaffected daughters. Then in 1828, Friedrich Hopff, a student at the University of Zurich, and his professor Dr. Schonlein, are credited with coining the term “haemorrhaphilia” for the condition, later shorted to “haemophilia.”

In 1926 Finnish physician Erik von Willebrand published a paper describing what he called “pseudohemophilia,” a bleeding disorder affecting men and women equally. It was later named von Willebrand disease. In 1957 Inga Marie Nilsson and researchers at the Malmo University Hospital in Sweden determined that VWD was caused by low levels or deficient von Willebrand factor.

In 1947, Dr. Alfredo Pavlovsky, a doctor in Buenos Aires, Argentina, distinguished two types of hemophilia in his lab—A and B.

Factor I deficiency was first described in 1920. Factors II and V deficiency were identified in the 1940s. The 1950s saw an explosion of work on rare factor deficiencies, as deficiencies of FVII, X, XI and XII were first recognized. In 1960, FXIII deficiency was described.

Source: https://www.hemophilia.org/Bleeding-Disorders/History-of-Bleeding-Disorders

[annaxbolina]

A classic petitio principii.

Me: What's pseudohemophilia?

Nicole: It's like hemophilia. But it's not hemophilia.

Me: X_X Thanks.

(Later)

Nicole: What do you mean by "opisthotonic"?

Me:Uhhh. May opisthotonism?XP