Haemophilia : Definition, Types, Pathogenesis, Clinical Features, Diagnosis, Treatment ( HD )

hello viewers I am dr. Reuben I work as a lecturer of pathology in a Medical College Hospital and I am making this video for my students and also for you hope someone finds this helpful today's topic is hemophilia in this video first we will try to define hemophilia then discuss its types pathogenesis and since hemophilia is a disorder of secondary hemostasis so we will briefly discuss about hemostasis followed by the clinical findings of hemophilia laboratory diagnosis treatment complications and prognosis of hemophilia okay so let's begin first question what is hemophilia the word hemophilia was derived from two ancient Greek word hi MA that means blood and philia that means affection or lust so the literal meaning of hemophilia is affection for blood or lusting for blood but don't confuse this thing with vampire okay no hemophilic patients are not vampire they don't have lust for blood as a matter of fact this thing is a misnomer the real meaning is different from the literal meaning so what is hemophilia then hemophilia can be defined as a common hereditary coagulation disorder due to deficiency or reduced activity of factor 8 or factor 9 okay so I'm repeating the definition again hemophilia can be as a common heritage haricots a Galatian disorder due to deficiency or reduced activity of clotting factor 8 or clotting factor 9 and one more thing you have to know that this disorder is x-linked recessive disorder okay so what do we mean by that that means like all other x-linked recessive disease the males will be the sufferer of this disease and the females the affected females will be the carrier of this disease and they usually will not show any symptom of hemophilia because they are having one healthy x chromosome and one x chromosome with the mutation however as we will see later that there is a term known as symptomatic female carrier and we will talk about that after a while and sometimes female can also become homozygous both X chromosomes mutated and in that case females may also develop hemophilia okay so the thing that you have to remember is no philia is an excellent recessive disorder and like all other x-linked recessive disease the males are the sufferer and the females the affected females are the carrier of this disease okay and to explain further about the x-linked recessive disease you can see that I have drawn a simple flowchart here and this will help you to understand the term x-linked recessive because you need to know this okay so suppose this is the mother she has two X chromosome and I have written one as X H because in that particular X chromosome the gene responsible for either clotting factor H or clotting factor 9 is mutated okay so that written as X H that is the mutated chromosome and the other chromosome is healthy this is the father you can see he has one X chromosome and one Y chromosome and you can see that these are the possible genotypes of their offspring so you can see that they will have they have chance of having a daughter like this and in this particular female you can see that she has one mutated X chromosome and one healthy X chromosome so according to the definition of recessive disease this will not show any symptom because when we are talking about recessive disease both genes must be mutated for that disease to occur okay so these will be the carriers hakama failure but look at this offspring this is a boy you can see that he has one x chromosome and unfortunately that x chromosome was the defective x chromosome that he got from his mother and he has one Y chromosome now the thing is since male have one x chromosome and one Y chromosome if that only X chromosome is mutated there is no second X chromosome to counter that mutation okay so therefore even with one mutated x chromosome the males become sufferer okay so that was the explanation why x-linked recessive disease causes disease in the male but the females are often seen as carrier okay so now that we have defined hemophilia now we will move on to the second part and that was the types of hemophilia so hemophilia can be of two type they are named hemophilia a and him philia beam when there is deficiency of the clotting factor 8 we call that hemophilia a and one thing you have to remember that hemophilia a was discovered first so hemophilia a is also known as the classical hemophilia and what about him affiliate B when there is deficiency of the clotting factor 9 which is also known as the Christmas factor we call that hemophilia B and as this is occurring due to deficiency of christmas' factor or clotting factor 9 so hemophilia B is also known as Christmas disease okay so those were the two types of hemophilia hemophilia A and hemophilia B now which one is common as a matter of fact hemophilia is a very rare disease hemophilia A is the incidence of hemophilia a is one in 10,000 population and hemophilia B is even more rare say for example about one in 50,000 or one in 100,000 operation in something like that okay so hemophilia A is the common one and hemophilia B is a very rare okay so now that we have discussed the definition and type of hemophilia now we will talk about the pathogenesis of hemophilia so like I said earlier hemophilia occurs due to deficiency of clotting factor H or clotting factor 9 and that deficiency is offering due to some genetic lesion in the genes responsible for making these clotting factors and those genes are located in the X chromosome the types of genetic lesions will include deletion nonsense mutation you know the type of mutation where stop codons are produced that is nonsense mutation that the energy relations may also include mutations that will cause error in mRNA splicing and the severe cases of hemophilia will occur due to inversion recall that inversion is a type of chromosomal rearrangement where a segment of chromosome is reversed end to end ok so that is the inversion and that type of genetic lesion with result in severe hemophilia if that inversion involves those genes that were needed to make factor 8 and factor 9 and as a matter of fact if there is inversion in those genes then there will be complete absence of factor 8 or factor 9 okay and there is also another type of genetic lesion that can cause mild haemophilia and that is a point mutation in those cases the level of factor 8 or factor 9 will appear normal however those factors will have reduced functionality okay and so that is briefly about the pathogenesis of hemophilia now before moving on to the next topic I would like to tell you three important informations because you will be often asked these questions in the examination the first question is will he Malik patients always give family history of hemophilia well you must be thinking that hemophilia is a x-linked recessive disease here the males are the sufferer and the females are the carrier so the patient may give history of similar symptoms in the male relatives of his maternal side of family and you are right in most of the cases however in thirty percent cases the patient will have no family history of hemophilia then how can you explain that thing the thing is in those thirty person cases hemophilia developed as a result of new mutation okay and that's why there is no family history in those cases but in most of the cases that patient will give a family history of male relatives on his maternal side of the family suffering from similar disease okay so that's the first point the second important point that I would like to mention is about symptomatic female carrier so I have already mentioned that in hemophilia females are not this supper they they are just the carrier of these disease okay but then how come sometimes the carriers themselves can develop mild haemophilia now recall that they are carrier okay so their genotype is like this one X chromosome has defect in the gene responsible for making factor eight and factor nine and the other factor eight are factor nine and the other X chromosome is normal so this is a genotype of a carrier of hemophilia and they should not have the disease because since hemophilia is the recessive disease both genes in both chromosome must be mutated for the disease to Express or or the disease to offer but then why are sometimes these carriers are becoming symptomatic although mild but symptomatic the answer lies in X chromosome inactivation well I have discussed in details about extra in activation in my previous video that was the molecular basis of cancer but to say in short during the blastocyst stage of development in female X chromosomes are randomly getting inactivated okay and what's happening in these cases the healthy X chromosome is getting inactivated in most of the cases and as a result so that is resulting in unfavorable X chromosome inactivation there is also a term for that that is unfavorable lionize ation and that is resulting in symptomatic female carrier of hemophilia okay so keep this a word in your mind symptomatic female carrier of emo philia they are carriers of hemophilia they have genotype like this and still they are showing mild haemophilia Y that is due to unfavorable X chromosome inactivation or unfavorable LAN ization and in that the healthy x chromosome is getting inactivated in most of the cases okay the third important point that you have to know is can female development failure yes females can develop hemophilia but to develop more failure in female there has to be homozygous mutation that means their genotype has to be something like this both x chromosome one came from the mother and one came from the father both must be mutated and this commonly occurs when there is a concern greeny T that is marriage between family members of the same affected hemophilic family say for example if the father had hemophilia and the mother was a carrier of him eeeh then they will have a daughter you know whose genotype will be something like this and to that daughter will develop hemophilia so now we will move on to the next point and that was regarding hemostasis now this is important in order to understand hemophilia we have to have some knowledge about hemostasis because those quantum factor 8 clotting factor 9 those were needed in secondary hues you spontaneous era stop bleeding okay and there are several steps that occur in order to stop our bleeding and as you can see I have drawn a simplified flowchart here so first there is a trauma and that will result in some disruption in the endothelium of the blood vessel and then blood will leak out and that is bleeding right and then what will happen will initially there will be some vasoconstriction you know and blood vessels in those affected area will become constricted okay and then what will happen then there will be formation of platelet plug and in order to understand the formation of platelet plug you can see that I have drawn another image here so in this image this is the blood vessels lumen these are the endothelium this is the nucleus of the endothelium and beneath the endothelium that I have drawn here in red this is the sub endothelial collagen this is also his sudden death he'll your collagen and I hope you can see these dots that I have drawn in the Sabbath ethereal collagen those are known as von Willebrand's factor okay so this part of the blood vessel has been damaged as you can see the endothelium has been disrupted and the von Willebrand factors that we're on the sub and ethereal collagen are now exposed then what will happen they will attract platelets you see these these I have drawn our platelet and they will come and they will attach with these von Willebrand factors in the southern with helium collagen and they will attach by using the GP 1b that is a glycoprotein GP 1b like a protein on the surface of the platelet and this is known as platelet adhesion okay so always remember a lot of my students get confused with the words platelet adhesion platelet aggregation so platelet adhesion occurs first then what will happen once the platelets are adhering with the von Willebrand factor and one muli one factor is in fact acting like a bridge between the southern ethereal collagen and the platelet so once the platelets through their gp1 be have bound with one will run factors in the southern ethereal collagen the platelets the platelets will get activated okay and the activated platelets will develop pseudopod as you can see I have drawn the activated platelets here in a larger scale okay so these I have drawn here in a zoomed out manner so look at these things they have developed silicones and they will form aggregation okay so more platelets will come and they will aggregate and they will use what is this thing this is fibrinogen or fibrinogen so they will use these big religions to act as cross link between these platelets and this is known as platelet aggregation okay so to say even in more details during platelet aggregation the platelets will express GP 2 B 3 a glycoprotein on their surface that is GP 2 B 3 a and those glycoproteins will cross link with Finnegan okay so they will use a Venusian to cross between more and more platelets and that is how the platelet plugs are produced okay so that was the second the thing happening in the platelets so first there was platelet adhesion and then there will be platelet aggregation and they will form a platelet plug but the problem is did this plug is unstable and in order to stabilize that platelet plug there lies the role of the clotting factors okay so that is the role of secondary hemostasis to make the unstable platelet plug stable and they do that by making fibrin okay so as you can see I have also drawn that here so the flagellation pathway will ultimately make fibrin and that will stabilize the platelet plugs now the last thing that I would like to mention regarding hemostasis is about the coagulation cascade because they are important for secondary hemostasis so in the coagulation cascade we have two pathways one is the intrinsic pathway and the other one is the extrinsic pathway and then there is the common coagulation pathway and we have different clotting factors in different pathways and you can have a lot of ways to remember this difficult pathway but the way I remember is I begin with 10 and I just think 5 multiplied by 2 is 10 and also 5 plus 2 is 7 so if I can know 10 5 to 7 then I just put the rest of the cutting factors on the other side and then I get these pathways ok so you can try that begin with 10 then think 5 times 2 is 10 5 plus 2 is so you put five here to here seven there and put rest of the clotting factors on the other side and this is the intrinsic pathway so the clotting factors 12:11 nine eight all are needed for the intrinsic pathway of the coagulation cascade similarly clotting factor seven is needed for extrinsic pathway and the reason I'm telling you this thing is we can get an idea about the defect whether that be kept is in the intrinsic pathway or in the extrinsic pathway by measuring PTT and Pt in the blood recall that PG means prothrombin time and prothrombin time gets elevated when there is some problem in the extrinsic pathway and PTT means partial thromboplastin time and partial thromboplastin time will get elevated if there is any problem in the intrinsic pathway okay and you can see that factor eight factor nine they fall in the intrinsic pathway so in case of mo failure as there is reduction in factor eight and after nine so the partial thromboplastin time will get elevated and the proton beam time will remain normal okay so that's the important point that you have to remember so now we will move on to the next topic and that was the clinical features of hemophilia so what are the clinical features of hemophilia patients with hemophilia can have bleeding for hours or even days after injury joint bleeding which is also known as he mitosis is a very common symptom in severe hemophilia patient the Communist science involved is the knee joint followed by elbow ankle joint shoulders and hips and wrist as Etra okay so science bleeding is very important clinical finding in hemophilia patient if the patient is a baby since babies have very sharp teeth and they tend to bite their gum and tongue so there may be bleeding from those sites for a long time and also there may be bleeding for a long time after tooth extraction another important clinical finding is bleeding from soft tissue and muscle say for example the iliopsoas muscle which is found around ah if there may be bleeding from that as well and intracranial hemorrhage all of pharyngeal hemorrhage these two are very rare symptom of hemophilia but when present they can be very dangerous now one thing you have to remember that the clinical severity of hemophilia correlates with the level of deficiency of the clotting factor say for example in case of hemophilia A if the level of clotting factor 80s below 1% of that of the normal level then there will be severe hemophilia if the level of factor 80s between 2% to 5% of that of the normal level of factor 8 then there will be moderating ophelia and if the level is between 6 percent to 50 percent of the normal level of the factor 8 then that will result in mild form of hemophilia so always keep that in your mind – so now we will move on and discuss the laboratory diagnosis of hemophilia so what are the laboratory findings that we will get in a patient of hemophilia so the blood coagulation time will be prolonged in severe cases only prothrombin time we'll be normal because recall that prothrombin time increases when there is detecting extrinsic pathway but factor 8 factor 9 they are located in the intrinsic pattern so proton beam time will be normal however apt T that is activated partial thromboplastin time will get elevated and then we have to do some special tests say for example factor 8 SI r factor 9 SI to further identify the hemophilia as hemophilia A or hemophilia B because we need to identify the deficient factor in order to treat hemophilia properly so now that we have discussed the laboratory diagnosis of lophelia briefly now we will move on and discuss the treatment of hemophilia if the patient has mild haemophilia then we can treat that with desmopressin acetate this drug increases the release of factor 8 from its storage site however if the patient has severe hemophilia then we have to infuse recombinant factor 8 to treat the patient okay so that is in short about the treatment of hemophilia and now we will move on to the next point and that is what are the complications of an untreated case of hemophilia now remember if I'm Ophelia is not treated then it can cause a lot of problems say for example in the joint the bleeding in the joint will result in joint damage there will be pain in the joint as well okay and there will be damage to the muscle sometimes there may be rarely a thing known as compartment syndrome in compartment syndrome there is bleeding inside the muscle and that gives pressure on the arteries and nerves inside the muscle and that may result in damage in the limbs okay there may be severe anemia and blood loss and there may be bleeding in the gastrointestinal tract and sometimes there is bleeding in the urinary tract that will result in immature Lia sometimes the blood can get caught it inside the urethra and in that case urine outflow may become obstructed and sometimes the patient may have a sharp pain in his lower abdomen so these are the complications of Mo philia sometimes in extremely rare cases there may be intracranial hemorrhage or bleeding from the oral pharyngeal cavity and those can be really dangerous so we are almost at the end of today's video regarding the prognosis of hemophilia if proper treatment is given and proper diagnosis is made the prognosis of hemophilia is good in most of the cases most of the patients of hemophilia can lead a normal life with the modern treatment available now problem arises when treatment was not given properly or the disease was not diagnosed properly in those cases the complications that I have mentioned a while ago can occur and also sometimes there may be a complication due to formation of inhibitors inhibitors are produced against the recombinant factor age or factor 9 that we use in the treatment of mo philia and those inhibitors are sometimes formed as a result of our body's immune response that is thinking those recombinant factor 8 or factor 9 as foreign substance in those cases treatment can become difficult so this concludes today's video on Murphy Leah for my students I hope you will go through your textbooks to know much more information about this topic and for my viewers thank you for watching this video for such a long time I hope this video was helpful I will try to upload a new video on von Willebrand's disease hopefully within a week until then take care and stay blessed and also if you like my videos do subscribe and comment in the comment sections below and let me know so take care and thank you you


  1. thank you ,my husband has himophilia now i understand it so much thank you again mr and mrs,rivera from meriden ct

  2. Sir, My query is that If "A" person (Male age 60) is suffering from heamophilia and his brother "B" (Male age 58) doesn't have heamophilia. If Son (Male age 29) of person "B" get married ( girl has pure background with whom he will get married) , can his offsprings have chances of getting suffer from heamophilia?

  3. I’m haemophiliac. Thank you for the lesson, I’ve learnt a lot. Keep on helping the nations retrieve their health to live longer and healthy. Regards

  4. Dear sir, i got job in Haemophilia pharmaceutical company after giving them successful interview of Haemophilia. It happened only because of you. I learned Haemophilia only thro your video

Leave a Reply

(*) Required, Your email will not be published