Hemophilia A

Chullin 87b ~ Talmudic Hematology

חולין פז, ב

אמר רב יהודה אמר שמואל כל מראה אדמומית מכפרין ומכשירין וחייבין בכסוי… ר' אסי מנהרביל אומר בצללתא דדמאי

Rav Yehuda says in the name of Shmuel: All mixtures of blood and water that maintain a reddish and render food susceptible to contracting ritual impurity, and are included in the obligation of covering the bloodhue are considered blood and effect atonement by being presented on the altar…Rabbi Asi of Neharbil says: The statement of Rav Yehuda is referring to the clear part of the blood [ i.e., plasma. If the plasma has a reddish hue due to the blood, it has the status of blood and can render food susceptible to contracting ritual impurity].

In today’s page of talmud we find one of the earliest references to a component of the blood known today as plasma. Here is how Rashi explains what Rav Yehuda was describing:

בצללתא דדמא - באותן מים שהם מן הדם עצמן כשהוא נקרש יש סביבותיו צלול כמים ואם יש

The clear part of the blood: The liquid that is part of the blood itself. When blood clots, it is surrounded by a clear liquid…

It took another couple of thousand years for us to understand the nature of this “clear part of the blood.” Here is what you need to know.

The components of Blood

From  here .

From here.

Sure, blood looks uniformly red, but if you let it stand (and not clot,) or better yet spin a sample in a centrifuge you will notice that to the naked eye it is made up of several components. At the bottom is a layer of dark red stuff, made up of red blood cells - you know, the ones that carry oxygen from the lungs around the body. On top of that is a thinner, lighter layer, made up of white blood cells that fight infection and platelets that are vital in forming blood clots. This layer is known as the buffy coat, from the word buff meaning yellowish (sort of like a manilla envelope). At the very top is a third layer with a yellowish tinge. We call that plasma, and it is what Rav Yehuda called צללתא דדמא.

What is plasma?

Plasma makes up about 55% of the blood volume, and serves several purposes. It is the medium that transports the red and white blood cells around the body, and it contains the clotting factors that well, make blood clot. Without them things can go badly for a baby boy at his circumcision (a topic we have addressed elsewhere). Plasma also contains immunoglobulins which fight infection, electrolytes, hormones and much else besides. But it cannot give you a better memory, prevent memory loss to serious diseases like dementia, improve Parkinson’s disease, or treat multiple sclerosis, heart disease or post-traumatic stress disorder. These are some of the claims of snake-oil type charlatans like this company. Just two days ago, the FDA issued a press statement alerting consumers and health care providers “that treatments using plasma from young donors have not gone through the rigorous testing that the FDA normally requires in order to confirm the therapeutic benefit of a product and to ensure its safety. As a result, the reported uses of these products should not be assumed to be safe or effective.”

Simply put, we’re concerned that some patients are being preyed upon by unscrupulous actors touting treatments of plasma from young donors as cures and remedies.
— FDA Press Announcement Feb 19, 2019.

(Legitimate) Plasma Donation

In the ER I would give whole blood to a patient who was leaking it out of a stab wound. But sometimes all you need to give is the plasma component. For example, in those with clotting deficiencies, plasma can stop life-threatening bleeds. That’s why it is important to donate whole blood (from which the plasma can be spun off) or just plasma (which takes longer to donate but which can be donated more frequently). If you live in the UK or, like me, lived in the UK in the 1980s, you can’t be a plasma donor, because of the fear of passing on a Creutzfeldt–Jakob like-disease, more commonly known as mad cow disease. In fact the UK imports all its plasma from the United States for this very reason.

For the rest of you who can donate, let the mention of plasma in today’s daf yomi prompt to go and donate some blood or plasma. Tell the medic you are donating in honor of page 87 of the Tractate Chullin. Rav Yehuda would be very proud.

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Chullin 4b~ Circumcision, Shechita, and Hemophilia A

In tomorrow’s page of Talmud, we are deeply engrossed in the question of who is qualified to be a shochet, one who slaughters food in accordance with Jewish law. A baraita (a set of oral teachings that never quite made it into the Mishnah) is quoted that teaches that an uncircumcised man may be a shochet. Then the Talmud asks:

חולין ד, ב

ה"ד אילימא מתו אחיו מחמת מילה האי ישראל מעליא הוא אלא פשיטא מומר לערלות וקא סבר מומר לדבר אחד לא הוי מומר לכל התורה כולה

This uncircumcised man, what are the circumstances? If we say that he is an uncircumcised man whose brothers died due to circumcision and the concern is that he might suffer a similar fate, clearly he may slaughter, as he is a full-fledged Jew and not a transgressor at all. Rather, it is obvious that he is a transgressor with regard to remaining uncircumcised, as he refuses to be circumcised, and the tanna holds that he may nevertheless slaughter an animal since a transgressor concerning one matter is not a transgressor concerning the entire Torah.

The Talmud here is referring to the sad case in which a mother loses her sons because they bleed to death following circumcision. In this encore presentation, let’s revisit the topic, which we first met way back in Yevamot 64a.

יבמות סד, א

תניא מלה הראשון ומת שני ומת שלישי לא תמול דברי רבי רבן שמעון בן גמליאל אומר שלישי תמול רביעי לא תמול... א"ר יוחנן מעשה בארבע אחיות בצפורי שמלה ראשונה ומת שניה ומת שלישית ומת רביעית באת לפני רבן שמעון בן גמליאל אמר לה אל תמולי

It was taught: If she circumcised her first son and he died, and her second son and he too died, she should not circumcise her third son, so taught Rebbi.  Rabbi Shimon ben Gamliel stated that she should indeed circumcise her third child, but [if he died] she must not circumcise her fourth...Rabbi Yochanan said that there was once a case in Zippori in which four sisters had sons:  The first sister circumcised her son and he died, the second sister circumcised her son and he died, the third sister circumcised her son and he died, and the forth sister came to Rabbi Shimon ben Gamliel and he told her "you must not circumcise your son" (Yevamot 64a).

The Talmud here is describing a disease that is affected through the maternal line (hence the four sisters - all of whom seem to pass this disease on to their male children). The disease is X-linked Hemophilia A; the term X-linked indicates that the faulty gene is carried on the X chromosome, which is men is always inherited from the mother. Hemophilia A is an X-linked recessive genetic disease, first described by the American physician John Conrad Otto, who in 1803 described a bleeding disorder that ran in families and mostly affected the men. John Hay from Massachusetts published an account of a "remarkable hemorrhagic disposition" in the New England Journal of Medicine in 1813.

Hay, John. Account of a Remarkable Haemorrhagic Disposition, Existing in Many Individuals of the Same Family.  New England Journal of Medicine  1813:2;3;221-225.

Hay, John. Account of a Remarkable Haemorrhagic Disposition, Existing in Many Individuals of the Same Family. New England Journal of Medicine 1813:2;3;221-225.

 If the mother is a carrier  - as were each of the four sisters in Zippori - then she has a one in four chance of passing on the disease to a child, and that affected child will always be a son:

Courtesy  NHLBI

Courtesy NHLBI

The rabbis argued over a technical point - that is, how many cases of bleeding are needed to establish a pattern. According to Rebbi (that is  Rebbi Yehuda Ha-Nasi, c. 135-217 CE.) two cases were sufficient, while Rabbi Shimon ben Gamliel insisted on three cases before ruling that there was a life threatening pattern.  Indeed the disease in boys must have been very perplexing, because (as you can see in the diagram above) not every boy would be affected. In fact, if the mother is a carrier and the father is not, there is only a 50% chance of a boy having hemophilia.  It is this fact that perhaps explains the dispute between Rebbi and Rabbi Shimon ben Gamliel regarding how many children need to exhibit the disease before we can assume that any future male child will also have it.  If every boy born in the family would have been a hemophiliac, Rabbi Shimon's ruling would have seemed unnecessarily cruel.  But since by chance, half of the boys born might not have hemophilia, the need to demonstrate the prevalence of the disease (in a society in which its genetic foundations were not known) seems eminently sensible.

In  Hemophilia A there are various genetic mutations that result in low levels of clotting factors. These levels may be only mildly decreased, or so low that severe life threatening hemophilia results. It is treated with transfusions of clotting factors which restore the levels to normal. Although these transfusions must be given several times a week in those with severe disease, there is hope that recombinant clotting factors can lengthen the time between the needed transfusions.

The hemophiliac as a shochet

The law discussed in Yevamot that forbids circumcision where there is a family history of hemophilia was certainly practiced. Later in Yevamot, the Mishnah records the case of a priest who was not circumcised -  because of the deaths of his brothers when they underwent the procedure. Tomorrow we read that a man who was not circumcised because he had hemophilia may serve as a shochet. The Talmud records not only the earliest known description of hemophilia, but the emphasis on the preservation of life as a normative Jewish practice. 

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Zevachim 22b ~ On the Physical and Mental Dangers of Circumcision

Milah knife..jpg

An uncircumcised Cohen may not, we are told in a Mishnah, offer sacrifices at the Temple in Jerusalem.  Just how did the Mishnah know this? In tomorrow's daf, we learn the answer:

זבחים כב,ב

 אמר רב חסדא דבר זה מתורת משה רבינו לא למדנו מדברי יחזקאל בן בוזי למדנו: כל בן נכר ערל לב וערל בשר לא יבא אל מקדשי לשרתני

Rav Chisdah says: We did not learn this matter from the Torah of Moses, our teacher; rather, we learned it from the words of the prophet Ezekiel, son of Buzi: “No stranger, uncircumcised in heart or uncircumcised in flesh, shall enter into My Sanctuary to serve Me” 

From the words "uncircumcised in flesh" the Talmud learns that a Cohen for whom circumcision would be life-threatening is forbidden to take part in sacrificial rites.  Earlier, (on page 15b) Rashi explains how circumcision might be dangerous:

 ערל. כהן שמתו אחיו מחמת מילה

Not circumcised: This means a Cohen whose brothers have died due to circumcision.

To understand the today's daf, we need to remind ourselves of the genetics of hemophilia. So let's go.

X-LINKED HEMOPHILIA A

The classic teaching about bleeding deaths and circumcision is found in Yevamot 64a.

יבמות סד, א 

תניא מלה הראשון ומת שני ומת שלישי לא תמול דברי רבי רבן שמעון בן גמליאל אומר שלישי תמול רביעי לא תמול... א"ר יוחנן מעשה בארבע אחיות בצפורי שמלה ראשונה ומת שניה ומת שלישית ומת רביעית באת לפני רבן שמעון בן גמליאל אמר לה אל תמולי

It was taught: If she circumcised her first son and he died, and her second son and he too died, she should not circumcise her third son, so taught Rebbi.  Rabbi Shimon ben Gamliel stated that she should indeed circumcise her third child, but [if he died] she must not circumcise her forth...Rabbi Yochanan said that there was once a case in Zippori in which four sisters had sons:  The first sister circumcised her son and he died, the second sister circumcised her son and he died, the third sister circumcised her son and he died, and the forth sister came to Rabbi Shimon ben Gamliel and he told her "you must not circumcise your son" (Yevamot 64:)

The Talmud here is describing a disease that is affected through the maternal line (hence the four sisters - all of whom seem to pass this disease on to their male children). The disease is X-linked Hemophilia A; the term X-linked indicates that the faulty gene is carried on the X chromosome, which is men is always inherited from the mother. Hemophilia A is an X-linked recessive genetic disease, first described by the American physician John Conrad Otto, who in 1803 described a bleeding disorder that ran in families and mostly affected the men. John Hay from Massachusetts published an account of a "remarkable hemorrhagic disposition" in the New England Journal of Medicine in 1813.

NEJM report of hemophilia 1813.png

If the mother is a carrier  - as were each of the four sisters in Zippori - then she has a one in four chance of passing on the disease to a child, and that affected child will always be a son:

In Yevamot, the rabbis argued over a technical point - that is, how many cases of bleeding are needed to establish a pattern. According to Rebbi (that is  Rebbi Yehuda Ha-Nasi, c. 135-217 CE.) two cases were sufficient, while Rabbi Shimon ben Gamliel insisted on three cases before ruling that there was a life threatening pattern.  Indeed the disease in boys must have been very perplexing, because (as you can see in the diagram above) not every boy would be affected. In fact, if the mother is a carrier and the father is not, there is only a 50% chance of a boy having hemophilia.  It is this fact that perhaps explains the dispute between Rebbi and Rabbi Shimon ben Gamliel regarding how many children need to exhibit the disease before we can assume that any future male child will also have it.  If every boy born in the family would have been a hemophiliac, Rabbi Shimon's ruling would have seemed unnecessarily cruel.  But since by chance, half of the boys born might not have hemophilia, the need to demonstrate the prevalence of the disease (in a society in which its genetic foundations were not known) seems eminently sensible.

In  Hemophilia A there are various genetic mutations that result in low levels of clotting factors. These levels may be only mildly decreased, or so low that severe life threatening hemophilia results. It is treated with transfusions of clotting factors which restore the levels to normal. Although these transfusions must be given several times a week in those with severe disease, there is hope that recombinant clotting factors can lengthen the time between the needed transfusions.

A Different explanation FROM Rabbenu Tam

In tomorrow's daf in Zevachim, we learn that there were indeed examples where what we call hemophilia A had been diagnosed, and as a result there were Cohanim who remained uncircumcised as adults. At least according to Rashi. But his grandson, Rabbenu Tam, has a different explanation. The Cohen did not have a clotting disorder. Rather, he was afraid of the pain of the procedure:

ערל. מפרש רבינו שלמה  בכל מקום שמתו אחיו מחמת מילה ור"ת מפרש דמומר לערלות וקרי ליה לבו לשמים לפי שאינו עושה אלא מדאגת צער המילה

According to Rabbenu Tam, this Cohen does not refuse circumcision as an act of religious rebellion. Rather, he refuses because of the pain involved in the procedure. Rabbenu Tam does not explain why the parents of the Cohen in question had not has him circumcised as a newborn - when he was in no position to object. But he makes a larger point: that a Jewish man who, out of fear, refuses to be circumcised - or to circumcise his newborn son - is not considered to be a religious rebel. Instead, he is called "one whose intentions are for the sake of heaven" - קרי ליה לבו לשמים.

Perhaps this expansive thinking of Rabbenu Tam might include today those who choose not to give their Jewish children a Brit Milah, because of concerns about informed consent.  Iceland recently introduced legislation to ban circumcision until a child reached the age of consent and could make an informed decision about his own genital future.  Rabbenu Tam would of course have wanted all Jewish newborn boys to have a Brit Milah and be welcomed into the Covenant of Abraham, but might he also understand those who felt differently?

[Partial repost from Repost from Yevamot 64a.]

Tagged: Hemophilia ACircumcision

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Avodah Zarah 27a ~ Circumcision and Hemophilia A

עבודה זרה כז, א

 ישראל שמתו אחיו מחמת מילה ולא מלוהו 

A Jew whose brothers died following their circumcisions, and was not circumcised.... 

fig1.jpg

In today's Daf Yomi, the Talmud considers whether a Jew who was not himself circumcised may serve as a mohel. This situation could arise when the newborn baby had older brothers who died from bleeding following their circumcisions. The young brother is then exempt from the mitzvah to be circumcised.

We first encountered this situation while studying Yevamot (64a) where cases of post-circumcision deaths are described. To understand the today's daf, we need to remind ourselves of the genetics of hemophilia.

X-linked Hemophilia A

יבמות סד, א 

תניא מלה הראשון ומת שני ומת שלישי לא תמול דברי רבי רבן שמעון בן גמליאל אומר שלישי תמול רביעי לא תמול... א"ר יוחנן מעשה בארבע אחיות בצפורי שמלה ראשונה ומת שניה ומת שלישית ומת רביעית באת לפני רבן שמעון בן גמליאל אמר לה אל תמולי

It was taught: If she circumcised her first son and he died, and her second son and he too died, she should not circumcise her third son, so taught Rebbi.  Rabbi Shimon ben Gamliel stated that she should indeed circumcise her third child, but [if he died] she must not circumcise her forth...Rabbi Yochanan said that there was once a case in Zippori in which four sisters had sons:  The first sister circumcised her son and he died, the second sister circumcised her son and he died, the third sister circumcised her son and he died, and the forth sister came to Rabbi Shimon ben Gamliel and he told her "you must not circumcise your son" (Yevamot 64:)

The Talmud here is describing a disease that is affected through the maternal line (hence the four sisters - all of whom seem to pass this disease on to their male children). The disease is X-linked Hemophilia A; the term X-linked indicates that the faulty gene is carried on the X chromosome, which is men is always inherited from the mother. Hemophilia A is an X-linked recessive genetic disease, first described by the American physician John Conrad Otto, who in 1803 described a bleeding disorder that ran in families and mostly affected the men. John Hay from Massachusetts published an account of a "remarkable hemorrhagic disposition" in the New England Journal of Medicine in 1813.

Hay, John. Account of a Remarkable Haemorrhagic Disposition, Existing in Many Individuals of the Same Family.  New England Journal of Medicine  1813:2;3;221-225.

Hay, John. Account of a Remarkable Haemorrhagic Disposition, Existing in Many Individuals of the Same Family. New England Journal of Medicine 1813:2;3;221-225.

 If the mother is a carrier  - as were each of the four sisters in Zippori - then she has a one in four chance of passing on the disease to a child, and that affected child will always be a son:

Courtesy  NHLBI

Courtesy NHLBI

In Yevamot, the rabbis argued over a technical point - that is, how many cases of bleeding are needed to establish a pattern. According to Rebbi (that is  Rebbi Yehuda Ha-Nasi, c. 135-217 CE.) two cases were sufficient, while Rabbi Shimon ben Gamliel insisted on three cases before ruling that there was a life threatening pattern.  Indeed the disease in boys must have been very perplexing, because (as you can see in the diagram above) not every boy would be affected. In fact, if the mother is a carrier and the father is not, there is only a 50% chance of a boy having hemophilia.  It is this fact that perhaps explains the dispute between Rebbi and Rabbi Shimon ben Gamliel regarding how many children need to exhibit the disease before we can assume that any future male child will also have it.  If every boy born in the family would have been a hemophiliac, Rabbi Shimon's ruling would have seemed unnecessarily cruel.  But since by chance, half of the boys born might not have hemophilia, the need to demonstrate the prevalence of the disease (in a society in which its genetic foundations were not known) seems eminently sensible.

In  Hemophilia A there are various genetic mutations that result in low levels of clotting factors. These levels may be only mildly decreased, or so low that severe life threatening hemophilia results. It is treated with transfusions of clotting factors which restore the levels to normal. Although these transfusions must be given several times a week in those with severe disease, there is hope that recombinant clotting factors can lengthen the time between the needed transfusions.

Later in Yevamot, the Mishnah records the case of a priest who was not circumcised -  because of the deaths of his brothers when they underwent the procedure. So this law was certainly practiced, and the Talmud records not only the earliest known description of hemophilia, but the emphasis on the preservation of life as a normative Jewish practice. 

רמב׳ם משנה תורה הל׳ מילה ב, א

הַכּל כְּשֵׁרִין לָמוּל. וַאֲפִלּוּ עָרֵל וְעֶבֶד וְאִשָּׁה וְקָטָן מָלִין בְּמָקוֹם שֶׁאֵין שָׁם אִישׁ

Everyone is qualified to perform the operation of circumcision. Where there is no adult circumcised male, (Israelite), it is performed by an uncircumcised Israelite, a bondman, a woman or a minor. 

[Repost from Yevamot 64a.]

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