Bleeding and Clotting Disorders: Haemophilia and Von Willebrand Disease

Haemophilia A, haemophilia B and von Willebrand disease are inherited disorders of haemostasis. Haemophilia reduces factor VIII or IX activity and classically causes joint, muscle and deep tissue bleeding. Von Willebrand disease impairs platelet adhesion and factor VIII stability, producing mainly mucosal bleeding, easy bruising and heavy menstrual bleeding.

What this lesson covers Bleeding disorders disturb one or more parts of normal haemostasis, the process that limits blood loss after vessel injury. Haemophilia A, haemophilia B and von Willebrand disease have different mechanisms, bleeding patterns and treatments. Haemophilia usually causes deep bleeding into joints, muscles and internal tissues because factor VIII or factor IX activity is deficient. Von Willebrand disease more often causes bleeding from the nose, mouth, skin, uterus and other mucosal surfaces because platelet adhesion is impaired. These are useful patterns rather than absolute rules. Severe von Willebrand disease can resemble haemophilia, and women and girls with haemophilia associated gene variants can have clinically important bleeding. Normal haemostasis Haemostasis begins within seconds of blood vessel injury and involves several overlapping processes. The injured vessel constricts, platelets adhere and aggregate to form an initial plug, and coagulation proteins generate fibrin that reinforces the plug. Natural anticoagulant and fibrinolytic systems limit the response to the injured area and later help remove the clot during healing. A problem with platelets or von Willebrand factor mainly disrupts the early plug. A major factor VIII or factor IX deficiency weakens fibrin generation and makes the initial plug less stable. Von Willebrand factor and platelet adhesion Von Willebrand factor, shortened to VWF, is a large adhesive protein produced mainly by endothelial cells and megakaryocytes. At an injured vessel, VWF attaches to exposed collagen and binds platelet receptors. It acts like a bridge that allows platelets to adhere despite flowing blood. This role is particularly important within small vessels and high shear areas, including the nose and other mucosal surfaces. Reduced or abnormal VWF therefore commonly causes nosebleeds, easy bruising, gum bleeding and heavy menstrual bleeding. The platelet plug After adhesion, platelets change shape and release chemical signals that recruit and activate additional platelets. Activated platelets bind to each other and build a temporary plug over the damaged area. They also provide a surface on which coagulation reactions occur efficiently. A low platelet count or impaired platelet function tends to cause immediate mucocutaneous bleeding, petechiae and bleeding from puncture sites. Haemophilia does not usually lower the platelet count or prevent the initial platelet plug from forming. The coagulation system Coagulation factors circulate mainly as inactive proteins. Vessel injury activates a series of reactions that culminate in the production of thrombin. Thrombin converts soluble fibrinogen into fibrin strands and activates factor XIII, which cross links and strengthens the fibrin network. Factor VIII works with activated factor IX to generate factor X activation efficiently. Deficiency of either factor markedly reduces thrombin production. The term coagulation cascade is useful, although haemostasis within the body occurs through interacting reactions on cell surfaces rather than a simple linear sequence. Why factor VIII and factor IX matter Factor VIII acts as a cofactor for activated factor IX. Together they greatly accelerate activation of factor X and the production of thrombin. Without enough factor VIII or factor IX, a platelet plug can form but may not receive enough fibrin reinforcement. Bleeding can restart after an apparently minor injury or continue deep within tissues even when the skin surface appears normal. Haemophilia A results from deficient or dysfunctional factor VIII. Haemophilia B results from deficient or dysfunctional factor IX. Fibrinolysis Once healing is underway, the fibrinolytic system helps break down fibrin through the enzyme plasmin. Mucosal tissues have substantial fibrinolytic activity, which is one reason mouth, nose and uterine bleeding can be difficult to control. Tranexamic acid slows fibrin breakdown and is particularly useful for many mucosal, dental and menstrual bleeds. It does not replace missing factor VIII, factor IX or VWF during a major bleed. It may also be unsuitable in selected urinary tract bleeding because retained clots can obstruct urine flow. Deep bleeding and mucocutaneous bleeding Coagulation factor deficiencies classically cause delayed or recurrent bleeding into joints, muscles and deep tissues. Large bruises and prolonged bleeding after surgery, dental extraction or trauma can occur. Platelet and VWF disorders classically cause nosebleeds, gum bleeding, easy bruising, prolonged bleeding from small cuts and heavy menstrual bleeding. This distinction is not absolute. Type 3 von Willebrand disease can reduce factor VIII substantially and cause joint or muscle bleeding. Routine coagulation tests A full blood count assesses haemoglobin and platelet number. It does not measure platelet function or exclude von Willebrand disease. The activated partial thromboplastin time, or APTT, assesses parts of the intrinsic and common coagulation pathways. It is often prolonged in moderate or severe haemophilia. The prothrombin time is usually normal in isolated haemophilia A or B. Both PT and APTT can be normal in mild haemophilia and many cases of von Willebrand disease. Normal screening tests must not overrule a convincing personal and family bleeding history. What haemophilia is Haemophilia is an inherited bleeding disorder caused by reduced activity of a specific coagulation factor. Haemophilia A is caused by changes affecting the F8 gene and factor VIII. Haemophilia B is caused by changes affecting the F9 gene and factor IX. Haemophilia A is more common, but the bleeding patterns of A and B are broadly similar at comparable factor levels. Neither disorder is caused by low platelets, and neither should be diagnosed from symptoms without factor testing. X linked inheritance The F8 and F9 genes lie on the X chromosome. Haemophilia A and B are therefore usually described as X linked inherited disorders. A boy or man with one affected X chromosome generally has haemophilia because there is no second X linked copy providing enough factor production. A woman with a haemophilia associated variant on one X chromosome may have a normal, reduced or very low factor level because X chromosome inactivation varies between cells. Inheritance language should not imply that women are always unaffected carriers. Some women and girls meet the clinical and laboratory definition of mild, moderate or severe haemophilia. Family inheritance patterns A man with haemophilia passes his affected X chromosome to all biological daughters and none of his biological sons. A woman with one haemophilia associated variant has a 50% chance in each pregnancy of passing that X chromosome to a child. A son who inherits it is usually affected. A daughter who inherits it may have carrier status or symptomatic haemophilia depending on factor activity. New genetic variants can occur, so haemophilia can appear without a previously recognised family history. Women and girls with haemophilia associated variants Women and girls may experience heavy menstrual bleeding, postpartum haemorrhage, easy bruising and prolonged bleeding after surgery or dental treatment. Factor levels should be measured rather than assuming that carrier status predicts bleeding risk. Rarely, a woman can inherit affected variants from both parents, have Turner syndrome or have very skewed X chromosome inactivation and develop severe disease. Care should be based on the person's factor level and bleeding phenotype, not sex alone. Severity classification Haemophilia severity is conventionally classified by baseline factor VIII or IX activity. Severe haemophilia means activity below 1 international unit per decilitre, equivalent to below 1%. Moderate haemophilia means activity from 1% to 5%. Mild haemophilia means activity above 5% and below 40%. The classification predicts average spontaneous bleeding risk but does not describe every person's individual bleeding pattern. Severe haemophilia Without effective prophylaxis, severe haemophilia commonly causes spontaneous joint and muscle bleeding from infancy or early childhood. Bleeding can follow an injury too minor to be remembered. Repeated episodes can produce target joints, chronic pain and disability. Intracranial, neck, chest, abdominal and iliopsoas bleeding can be life threatening. Modern prophylaxis aims to prevent spontaneous bleeding and preserve normal joint development rather than waiting for repeated bleeds to occur. Moderate haemophilia Moderate haemophilia can cause occasional spontaneous bleeding and prolonged bleeding after relatively minor injury. Some people have a severe clinical phenotype despite a factor level within the moderate range, while others bleed mainly around procedures. The personal bleeding pattern, joint health, activity and access to rapid treatment guide whether continuing prophylaxis is appropriate. The label moderate does not mean that head injury or internal bleeding is safe. Mild haemophilia Mild haemophilia may remain unrecognised until surgery, dental extraction, childbirth or significant trauma. Spontaneous joint bleeding is uncommon, but serious procedural or traumatic bleeding can occur. The APTT can be normal, particularly when factor activity is near the upper end of the mild range. A known diagnosis should be documented clearly before any invasive procedure because ordinary surgical protocols may not provide adequate haemostatic cover. Factor level is not the whole phenotype People with the same baseline factor level can have different bleeding frequencies and joint outcomes. The genetic variant, joint history, physical activity, other medicines and individual coagulation characteristics can contribute. An inhibitor can abruptly make replacement treatment ineffective and worsen bleeding. Specialist teams therefore monitor actual bleeds, joint health and treatment response rather than relying only on one factor percentage. Haemarthrosis Haemarthrosis means bleeding into a joint and is the hallmark bleeding pattern of haemophilia. The ankles, knees and elbows are common sites because they experience frequent mechanical loading. Hips, shoulders and other joints can also bleed. Early features include tingling, warmth, fullness or an unusual sensation before obvious swelling develops. Pain, reduced movement and a flexed resting position can follow. Treatment is most effective when the person's prescribed haemostatic therapy is given at the first recognised symptoms rather than after major swelling appears. What blood does inside a joint Blood within a joint irritates the synovial lining and releases iron containing breakdown products. Inflammation causes synovial thickening and increased blood vessel formation, making further bleeding more likely. Repeated cycles damage cartilage and the bone beneath it. A joint that bleeds repeatedly is called a target joint. Without adequate prevention and rehabilitation, chronic haemophilic arthropathy develops. Haemophilic arthropathy Haemophilic arthropathy is chronic joint disease caused by recurrent haemarthroses and inflammation. It can produce persistent pain, stiffness, reduced movement, muscle weakness, altered walking and deformity. Prophylaxis started early in life has transformed joint outcomes, but people treated later may already have established damage. Physiotherapy, strength work, pain management, imaging and selected orthopaedic procedures form part of comprehensive care. Muscle bleeding Muscle bleeds cause pain, swelling, reduced movement and sometimes nerve or blood vessel compression. Bleeding into the forearm or calf can raise pressure within a closed fascial compartment and threaten nerves and circulation. Deep muscle bleeds may be difficult to see externally. A falling haemoglobin or progressive weakness can be the first clue. Haemostatic treatment should begin promptly, with imaging and surgical or orthopaedic assessment when compartment syndrome is suspected. Iliopsoas bleeding The iliopsoas is a deep muscle within the abdomen and pelvis. Bleeding can cause lower abdominal, groin, hip or back pain. The person may keep the hip flexed because extension increases pain. Femoral nerve compression can cause numbness or weakness in the front of the thigh and reduced knee reflexes. The bleed can hold a large volume of blood without visible bruising and requires urgent factor treatment, imaging and specialist management. Intracranial bleeding Bleeding inside the skull is a true emergency in any bleeding disorder. It can follow an obvious head injury or develop after apparently minor trauma. Symptoms include worsening headache, repeated vomiting, drowsiness, confusion, seizure, unequal pupils, weakness, speech change or loss of consciousness. In known haemophilia, prescribed factor or emergency haemostatic treatment is given immediately when intracranial bleeding is suspected and should not wait for imaging confirmation. Neck, throat and airway bleeding Bleeding into the tongue, floor of the mouth, throat or neck can compress the airway. Warning symptoms include neck swelling, difficulty swallowing, a changed voice, drooling, noisy breathing or breathlessness. This requires immediate emergency haemostatic treatment and airway assessment. Repeated throat examination or unnecessary instrumentation can worsen bleeding and should be undertaken only by an appropriate emergency team. Dental, surgical and post traumatic bleeding Mild haemophilia may first become apparent through prolonged bleeding after tooth extraction, tonsil surgery, circumcision or another procedure. Bleeding can begin after an initial clot appears because the fibrin reinforcement is insufficient. Every dental extraction, operation, endoscopy, biopsy or regional anaesthetic should be planned with the haemophilia centre. The plan may combine factor replacement, desmopressin, tranexamic acid and local haemostatic measures according to the diagnosis and procedure. Other internal bleeding Gastrointestinal bleeding can cause vomiting blood, black stool, abdominal pain, anaemia or collapse. Urinary tract bleeding can cause visible blood, flank pain and clots. Tranexamic acid is used cautiously or avoided in upper urinary bleeding because obstructing clots can form. Retroperitoneal bleeding can cause abdominal, back or groin pain and circulatory compromise without visible external bleeding. A bleeding disorder diagnosis must not prevent investigation for ulcers, cancer, stones or another underlying source. Diagnosing haemophilia Diagnosis uses a personal and family bleeding history, coagulation screening and specific factor assays. Factor VIII activity identifies haemophilia A after von Willebrand disease and acquired causes are considered. Factor IX activity identifies haemophilia B. Mixing studies can help distinguish a factor deficiency from an inhibitor when the APTT is prolonged. Genetic testing identifies the F8 or F9 variant in many families and supports carrier testing, reproductive counselling and inhibitor risk assessment. New diagnosis without family history A substantial minority of haemophilia cases arise without a previously recognised family history. This can result from a new genetic variant, an unrecognised affected relative or limited information about maternal family members. A child with unexplained joint or muscle bleeding, excessive bleeding after a procedure or an isolated prolonged APTT requires appropriate investigation. Safeguarding assessment and medical investigation can both be necessary when unexplained bruising occurs in a child. One should not replace the other. Genetic counselling and carrier testing Once a family variant is known, at risk relatives can be offered genetic counselling and testing. Testing clarifies reproductive risk but does not replace measurement of factor VIII or IX because bleeding risk depends on actual activity. Counselling explains inheritance, uncertainty, confidentiality and options without directing reproductive decisions. Prenatal diagnosis and preimplantation genetic testing may be available to families who wish to consider them. Pregnancy in haemophilia carriers Pregnancy can raise factor VIII but does not reliably correct low factor IX. Factor levels are checked during pregnancy and when delivery planning is finalised. The maternity, anaesthetic, obstetric and haemophilia teams agree plans for neuraxial anaesthesia, delivery, factor support and newborn testing. Instrumental delivery and fetal scalp procedures may be avoided when the fetus could have haemophilia, depending on the clinical circumstances. Factor levels can fall after birth, so primary and delayed postpartum haemorrhage remain important risks. Factor replacement Factor replacement supplies the missing coagulation protein through intravenous infusion. Haemophilia A uses factor VIII concentrate, while haemophilia B uses factor IX concentrate. Recombinant and plasma derived products are available, with standard and extended half life options. The dose depends on body weight, current factor level, target level, product recovery and the bleeding site or procedure. On demand treatment On demand treatment means giving haemostatic therapy when a bleed occurs or around a specific injury or procedure. It can be appropriate for some people with mild haemophilia and selected people with infrequent bleeding. In severe haemophilia, relying only on on demand treatment allows repeated clinical and subclinical joint bleeding and does not provide optimal joint protection. Even with regular prophylaxis, breakthrough bleeds need a specific on demand plan. Prophylaxis Prophylaxis means regular treatment intended to prevent bleeding before it begins. Factor prophylaxis maintains factor activity above an individualised protective level. Modern regimens use pharmacokinetic information, bleed history, activity and joint condition rather than one schedule for everyone. Severe haemophilia A may be treated with factor VIII prophylaxis or emicizumab. Severe haemophilia B usually uses factor IX prophylaxis, with additional newer options available in selected pathways. The goal is a life with minimal spontaneous bleeding and preserved physical function. Home treatment and bleed plans Home treatment reduces delay between recognising a bleed and receiving therapy. The haemophilia centre teaches preparation, infusion, dose recording, storage and safe disposal. Families also learn when home treatment is insufficient. Head injury, neck swelling, major trauma, severe abdominal pain, uncontrolled bleeding and neurological symptoms still require emergency assessment. Treatment records help the centre identify breakthrough patterns, adherence barriers and possible inhibitor development. Desmopressin in haemophilia A Desmopressin, also called DDAVP, releases stored VWF and factor VIII from endothelial cells. It can raise factor VIII sufficiently for selected bleeds or procedures in some people with mild haemophilia A. A supervised response test is usually performed before relying on it. It does not treat haemophilia B and is ineffective in severe haemophilia A when there is too little releasable factor VIII. Repeated doses can become less effective and can cause water retention and hyponatraemia, so fluid guidance and dose limits are essential. Tranexamic acid in haemophilia Tranexamic acid stabilises fibrin by reducing its breakdown. It is particularly useful for dental, oral, nasal and other mucosal bleeding and is often combined with factor treatment or desmopressin. It does not provide adequate sole treatment for a major joint, muscle or intracranial bleed. Kidney function, thrombosis history and urinary tract bleeding affect whether and how it is used. Emicizumab Emicizumab is a subcutaneous bispecific monoclonal antibody used for prophylaxis in haemophilia A. It brings activated factor IX and factor X into proximity and mimics an important cofactor function of activated factor VIII. It is not factor VIII and cannot be measured or managed using ordinary factor VIII assumptions. It prevents bleeding in people with or without factor VIII inhibitors, but breakthrough bleeds and surgery still require a specialist plan. Other non factor and newer treatments Newer prophylactic medicines rebalance coagulation without replacing factor VIII or IX directly. Some inhibit natural anticoagulant pathways such as tissue factor pathway inhibitor. Their indications differ according to haemophilia type, age and inhibitor status. Gene therapy can enable the liver to produce factor VIII or IX in selected adults, but response and durability vary and long term monitoring is required. These treatments broaden choice but do not eliminate the need for emergency plans, joint surveillance or specialist follow up. Factor inhibitors An inhibitor is an antibody that neutralises infused factor VIII or factor IX. Inhibitors occur most often during early exposure in severe haemophilia A, although they can develop later and in non severe haemophilia. Factor IX inhibitors are less common but can be associated with severe allergic reactions. A bleed that responds poorly to the usual factor dose or an unexpectedly low laboratory recovery raises concern about an inhibitor. Treating haemophilia with inhibitors When factor VIII or IX is neutralised, ordinary replacement may not control bleeding. Bypassing agents such as recombinant activated factor VII or activated prothrombin complex concentrate can generate haemostasis without relying on the missing factor. Emicizumab provides prophylaxis for haemophilia A with inhibitors. Breakthrough treatment must follow a specialist protocol because combining emicizumab with high cumulative activated prothrombin complex doses can cause thrombosis or thrombotic microangiopathy. Immune tolerance induction Immune tolerance induction uses repeated factor exposure to help eradicate some factor VIII inhibitors. The regimen can continue for many months and requires regular inhibitor and factor recovery monitoring. Success can allow ordinary factor VIII treatment to work again. Treatment burden, venous access, breakthrough bleeding and family circumstances are addressed by the specialist team. Planning surgery and dentistry The haemophilia centre calculates the required haemostatic level before, during and after a procedure. Major surgery needs laboratory monitoring and several days of treatment. Minor dental work may use local measures and tranexamic acid, while extraction can require factor or desmopressin cover. The surgeon, dentist, anaesthetist and laboratory must know about inhibitors, emicizumab and previous treatment reactions. Exercise and joint protection Regular physical activity strengthens muscles, supports joints, improves bone health and reduces deconditioning. Inactivity is not a safe long term strategy. Lower impact and non contact activities are often easier to undertake safely, but individual choice depends on proficiency, prophylaxis, joint health and protective equipment. Physiotherapy helps restore movement after a bleed and identify early joint deterioration. Contact or high trauma sports require discussion with the haemophilia team rather than a universal prohibition or false reassurance. What von Willebrand disease is Von Willebrand disease, shortened to VWD, is the commonest inherited bleeding disorder. It results from too little VWF or from VWF that does not function normally. Clinical severity ranges from mild bleeding noticed only after surgery to severe spontaneous mucosal, gastrointestinal, joint or muscle bleeding. Both women and men can inherit and express VWD, and heavy menstrual bleeding makes the disorder particularly important in reproductive healthcare. The two roles of von Willebrand factor VWF has two central haemostatic roles. First, it enables platelets to adhere to damaged vessel walls and supports platelet aggregation under flowing conditions. Second, it binds and protects factor VIII from rapid clearance in the circulation. Severe VWF deficiency therefore impairs primary platelet adhesion and can also produce low factor VIII activity, creating a combined mucocutaneous and deep bleeding phenotype. Inheritance of von Willebrand disease Most type 1 VWD and many type 2 forms are inherited in an autosomal dominant pattern, although penetrance and bleeding severity vary. Type 3 VWD is usually autosomal recessive and can occur when a child inherits a severely affected VWF gene from each parent. Some type 2 variants have different inheritance patterns, and not every person with a low VWF result has a clearly identifiable pathogenic variant. Family testing is guided by the subtype, genetic result and bleeding history. Type 1 von Willebrand disease Type 1 VWD is a partial quantitative deficiency. VWF is structurally capable of working, but the amount available is reduced. It is the commonest diagnosed type and usually causes mild to moderate mucocutaneous bleeding. Levels and bleeding can vary within the same family. Age, stress, pregnancy, inflammation and blood group influence measured VWF, so treatment is tailored to actual bleeding and procedural risk. Type 2 von Willebrand disease Type 2 VWD is a qualitative disorder in which VWF is present but works abnormally. Subtypes affect multimer structure, platelet binding or factor VIII binding in different ways. This influences whether desmopressin is useful or potentially unsuitable. Type 2B VWD can cause or worsen thrombocytopenia because abnormal VWF binds platelets too readily. Type 2N mainly impairs factor VIII binding and can resemble mild haemophilia A without careful specialist testing. Type 3 von Willebrand disease Type 3 VWD involves virtually absent VWF and is the rarest major type. Factor VIII can be very low because its carrier protein is missing. Bleeding can include severe nose or mouth bleeding, gastrointestinal bleeding, haemarthrosis and muscle bleeding. Desmopressin is ineffective because there is little or no stored VWF to release, so VWF containing concentrate is central to treatment and prophylaxis. Mucocutaneous bleeding in VWD Common features include recurrent nosebleeds, easy bruising, gum bleeding and prolonged bleeding from minor wounds. Bleeding after dental extraction, tonsil surgery and other mucosal procedures can be disproportionate to the apparent injury. Some people have gastrointestinal bleeding, particularly with angiodysplasia in selected VWD types. Symptoms are often normalised within families because several relatives may have always experienced similar bleeding. Heavy menstrual bleeding Heavy menstrual bleeding is an important and under recognised presentation of VWD and other inherited bleeding disorders. Clues include flooding, passing large clots, changing protection during the night, bleeding through clothing, periods lasting more than seven days and iron deficiency. Heavy bleeding from the first menstrual periods, a family history and bleeding after dental work or childbirth increase suspicion. The symptom should not be dismissed as normal, and gynaecological causes can coexist with a bleeding disorder. Iron deficiency from menstrual bleeding Repeated menstrual blood loss can exhaust iron stores before haemoglobin becomes low. Fatigue, reduced concentration, restless legs, hair shedding and reduced exercise tolerance can occur with iron deficiency. A full blood count and ferritin form part of assessment, with oral or intravenous iron used according to severity and tolerance. Replacing iron is necessary but does not control the bleeding source or establish whether VWD is present. Pregnancy and postpartum bleeding in VWD VWF and factor VIII usually rise during pregnancy, particularly in type 1 VWD, but the response is variable and may be inadequate in type 2 or type 3 disease. Levels are checked during pregnancy so delivery, anaesthesia and postpartum haemostasis can be planned. After birth, VWF and factor VIII fall towards baseline, creating a risk of delayed postpartum haemorrhage after hospital discharge. Tranexamic acid, desmopressin or VWF concentrate may be used according to subtype, levels and the specialist plan. Diagnosing von Willebrand disease Diagnosis begins with a structured personal and family bleeding history and exclusion of acquired causes. Laboratory testing includes VWF antigen, a platelet binding VWF activity assay and factor VIII activity. The relationship between antigen and activity helps identify qualitative type 2 patterns. Further tests can include multimer analysis, collagen binding, platelet binding studies, factor VIII binding assays and genetic testing. Why VWF testing may need repeating VWF is an acute phase reactant and rises during stress, exercise, inflammation, trauma, pregnancy and oestrogen exposure. Testing during active severe bleeding or anaemia can therefore produce a falsely reassuring level. People with blood group O have lower average VWF levels than people with many other ABO groups, but blood group does not itself diagnose disease. Borderline or discordant results are often repeated when health is at baseline and interpreted alongside the bleeding history. Desmopressin in VWD Desmopressin releases stored VWF and factor VIII and can control selected bleeds in responsive type 1 and some type 2 VWD. A trial establishes whether VWF and factor VIII rise sufficiently and remain adequate for the required period. It is ineffective in type 3 VWD and is generally avoided in type 2B because it can worsen thrombocytopenia. Fluid restriction and sodium monitoring help prevent dangerous hyponatraemia, particularly in children and during repeated dosing. VWF containing concentrates VWF containing concentrate replaces missing or defective VWF directly. Some products also contain factor VIII, while recombinant VWF contains VWF without plasma derived factor VIII. Concentrate is used for severe bleeding, major surgery, type 3 VWD and situations where desmopressin is ineffective or unsuitable. The team monitors VWF and factor VIII because repeated treatment can raise factor VIII and potentially increase thrombosis risk. Tranexamic acid in VWD Tranexamic acid is a major treatment for nose, mouth, dental and menstrual bleeding in VWD. It can be taken alone for mild mucosal bleeding or combined with desmopressin or VWF concentrate. Dose and duration depend on age, kidney function, the bleeding site and thrombosis history. Visible urinary bleeding requires specialist advice before use because clots can obstruct the urinary tract. Managing heavy menstrual bleeding Management combines control of blood loss, correction of iron deficiency and treatment of any gynaecological condition. Options include tranexamic acid during menstruation, combined hormonal contraception, progestogen treatment and a levonorgestrel releasing intrauterine system. Desmopressin or VWF concentrate can be used in selected situations according to the VWD type and response. Haematology and gynaecology should work together when bleeding is severe, fertility is relevant or first line treatment is ineffective. Acquired bleeding disorders Not every factor deficiency is inherited. Acquired haemophilia A results from autoantibodies against factor VIII and can cause extensive skin, muscle, gastrointestinal or postpartum bleeding in someone without a previous personal or family history. Acquired VWD can occur with selected cardiac, autoimmune, thyroid or haematological disorders. New severe bleeding with an isolated prolonged APTT or unexpected VWF abnormality requires urgent specialist investigation rather than family based assumptions. Thrombophilia as the conceptual opposite Bleeding disorders reduce effective haemostasis, while thrombophilia shifts the balance towards inappropriate clot formation. Inherited thrombophilias and antiphospholipid syndrome are discussed in greater depth in the venous thromboembolism lesson. A person can occasionally have both a bleeding disorder and a thrombosis risk, particularly with age, surgery, replacement treatment, central lines or another medical condition. Neither diagnosis automatically cancels the other, so anticoagulation and haemostatic treatment require specialist balancing. Aspirin and NSAIDs Aspirin irreversibly impairs platelet function and can significantly increase bleeding. Traditional NSAIDs such as ibuprofen, naproxen and diclofenac also impair platelet function and can cause gastrointestinal bleeding. They are generally avoided unless the bleeding disorder team has advised a specific regimen. Paracetamol is often a safer first analgesic, although dose limits and liver health still matter. Aspirin or anticoagulation may occasionally be essential for cardiovascular disease, but the decision should involve haematology rather than unsupervised stopping or continuation. Intramuscular injections and vaccination Unnecessary intramuscular injections are avoided because they can cause muscle haematoma. Essential vaccination should not be withheld. Depending on the vaccine and bleeding severity, it can be given subcutaneously when permitted or intramuscularly with a fine needle, appropriate haemostatic timing and firm pressure afterwards. The injection site should not be rubbed, and new swelling or severe pain requires advice. Vaccination plans should include relevant routine and additional protection according to national and specialist guidance. Venepuncture and routine procedures Blood sampling is usually safe with an experienced practitioner, an appropriate needle and firm pressure for longer than usual. Arterial puncture, lumbar puncture, biopsy, endoscopy and regional anaesthesia require specific haemostatic planning. A normal appearance immediately after a procedure does not prove that delayed bleeding will not occur. The person should receive written instructions about treatment, observation and when to return urgently. Emergency cards and medical alerts People with haemophilia, significant VWD or inhibitors should carry an up to date bleeding disorder card or medical alert. It should state the diagnosis, baseline factor level, inhibitor status, current prophylaxis, emergency product and haemophilia centre contact details. Emergency clinicians should contact the specialist centre but should not delay immediate haemostatic treatment for a suspected life threatening bleed. A general label such as bleeding tendency is insufficient because factor VIII, factor IX, VWF and inhibitor pathways require different products. Living with a bleeding disorder Modern prophylaxis and coordinated care allow most people to attend school, work, exercise, have relationships and plan families. The disorder can still impose infusion burden, pain, fatigue, anxiety and concern about emergencies or procedures. Psychological care, physiotherapy, dental support, reproductive care and social or educational adjustments form part of comprehensive treatment. The person's expertise in recognising their own bleeds should be respected while new or unusual symptoms are assessed objectively. Prognosis Early diagnosis, safe factor products, prophylaxis and comprehensive haemophilia care have transformed survival and joint outcomes. Inhibitors, delayed treatment and established arthropathy can still cause substantial illness and disability. Most people with type 1 VWD have a normal life expectancy, but bleeding can significantly affect menstruation, childbirth, surgery and quality of life. Type 3 VWD and severe qualitative variants require lifelong specialist management similar in intensity to other severe bleeding disorders. Follow up Regular review records bleeding frequency, joint health, treatment adherence, inhibitor testing, product response and adverse effects. Women and girls should be asked directly about menstruation, iron deficiency, pregnancy and postpartum bleeding rather than waiting for them to volunteer symptoms. Children need growth, activity and developmental support, while adults require cardiovascular, bone, pain and ageing related assessment. Any change in bleeding pattern should prompt reassessment for an inhibitor, new medicine, liver disease, acquired disorder or another source of bleeding. The central safety message Haemophilia causes deficient factor VIII or IX activity and classically produces deep joint and muscle bleeding. Von Willebrand disease disrupts platelet adhesion and factor VIII stability and more often causes mucocutaneous bleeding. Known haemophilia with suspected intracranial, neck, major muscle or other life threatening bleeding requires immediate haemostatic treatment before diagnostic delay. Heavy menstrual bleeding can be the first sign of an inherited bleeding disorder and should not be normalised or dismissed.

Bleeding pattern gives an important clue but not a final diagnosis. Haemophilia usually causes deep bleeding because factor VIII or IX is deficient, while von Willebrand disease usually causes mucocutaneous bleeding because VWF supports both platelet adhesion and factor VIII survival. Life threatening bleeding is treated immediately according to the person's specialist plan.