Year : 2011 | Volume
: 4 | Issue : 2 | Page : 292--298
Revisiting hemophilia management in acute medicine
Sandeep Sahu1, Indu Lata2, Surendra Singh1, Mukesh Kumar3,
1 Department of Anaesthesiology, Maternal &Reproductive Health and Neurosurgery (Neuro-Otorhinology), Lucknow, UP, India
2 Maternal &Reproductive Health and Neurosurgery (Neuro-Otorhinology), Lucknow, UP, India
3 Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, UP, India
Department of Anaesthesiology, Maternal &Reproductive Health and Neurosurgery (Neuro-Otorhinology), Lucknow, UP
The World Federation of Hemophilia estimates that more than 350,000 people globally have a form of the disease. Hemophilia A is a bleeding disorder that has a spectrum of manifestations ranging from persistent bleeding after minor trauma to spontaneous hemorrhage. We report a case of a male patient with hemophilia A who received general anesthesia for removal of foreign body from the nose. There was no excessive blood loss during surgery. Perioperatively, the patient received recombinant factor VIII coverage. Rest of the postoperative course was uneventful. Literature on the clinical management of patient with hemophilia A are reviewed and considerations for perioperative preparation and management of hemophilic patient are presented.
|How to cite this article:|
Sahu S, Lata I, Singh S, Kumar M. Revisiting hemophilia management in acute medicine.J Emerg Trauma Shock 2011;4:292-298
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Sahu S, Lata I, Singh S, Kumar M. Revisiting hemophilia management in acute medicine. J Emerg Trauma Shock [serial online] 2011 [cited 2019 Jun 18 ];4:292-298
Available from: http://www.onlinejets.org/text.asp?2011/4/2/292/82225
Hemophilia is a bleeding disorder characterized by prolonged blood clotting time. Individuals with hemophilia have deficient or defective coagulation proteins in their blood, which causes excessive bleeding from even minor injuries. The two most common forms of hemophilia are:
Hemophilia A - characterized by deficient or defective clotting factor VIII.Hemophilia B - caused by deficient or defective clotting factor IX.
Before the advent of modern blood banking, the mortality and morbidity from hemophilia was much higher. Now-a-days, recurrent bleeding episodes, painful hemarthrosis and permanent disability secondary to ankylosed joints increased morbidity in hemophilic patients.  Surgical option for even a mild ailment was impossible as a dental extraction could become a life-threatening event. Use of a recombinant factor VIII concentrate for treatment has greatly revolutionized the management of hemophilia patients.
A 4-year-old male child having severe hemophilia A (recurrent epistaxis, bleeding from gums, echymosis and easy bruisability in the past) on regular treatment and follow-up in the hematology department of the institute was referred to the ENT OPD with the chief complaints of foul-smelling nasal discharge and persistent excessive sneezing for 2 months. He had suffered from one recent episode of upper respiratory tract infection. He was getting supplemental iron tablets and had received IV recombinant factor VIII once in the past.
An infected growth, bacterial or fungal sinusitis or foreign body (FB) in the nose was suspected. An X-ray of the paranasal sinuses revealed an irregular soft tissue density in the left (L) maxillary sinus. A computed tomography (CT) scan of the paranasal sinuses confirmed the presence of FB. Laboratory investigations performed were serum creatinine 0.6 mg%, B + blood group, Hb 11.8 gm%, TLC 10,400 (P 66 L 29 E 1 ), normocytic and normochromic general blood picture, reticulocyte count (0.8%), mean corpuscular hemoglobin (MCH) 78.7%,mean corpuscular hemo concentration (MCHC) 32%, platelet (4.1 lakhs) and prothrombin time (PT) 12.6/11.8 s. Raised aPTT (1 min 28 s/29.7 s) was the only significant finding. Factor VIII was 0% and no inhibitor against factor VIII was found.
The patient was jointly reviewed by an ENT surgeon, an anesthesiologist, a hematologist and a pediatrician and a management strategy was charted out. In view of the tender age and severe bleeding disorder hemophilia, it was decided to remove the FB under general anesthesia with a secure airway. To prevent excessive perioperative bleeding, 30 U/kg of human recombinant factor VIII was administered IV (one vial having 220-400 monoclonal purified activity units in Hemofil-M, Baxter product code, 1501805) 1 h before operation. In the operation theater, one more IV line was established for drugs and fluids while the other was reserved for factor VIII infusion. Injection tranexamic acid 150 mg was given as infusion before the induction of anesthesia. Colloids, packed red cells and fresh frozen plasma (FFP) were kept at hand. Anesthesia was induced with thiopental (3 mg/kg) and endotracheal intubation (4.5 mm cuffed endotracheal tube) was performed after achieving paralysis with 25 mg of succinylcholine. A throat pack was gently inserted, avoiding any trauma, to prevent aspiration. Vecuronium bromide 1.5 mg was used after recurrence of respiratory efforts.
Using a flexible endoscope, the FB was successfully removed in 10 min without any bleeding. Extra care was taken to avoid even minimal trauma. Residual muscle paralysis was reversed with neostigmine and glycopyrrolate. Before extubation, the oral and nasal cavities were carefully examined for any active bleeding by both the surgeon and the anesthesiologist. After extubation, the patient was shifted to the intensive care unit and nursed in the recovery position. Six hours after surgery, the patient received another vial of factor VIII and one vial once a day thereafter for 4 days. The postoperative period was uneventful. After 7 days, the patient was discharged from the hospital.
Management of this diagnosed case of severe hemophilia-A with FB in the nose is an opportunity to discuss other important pearls regarding severe hemophilia. Hemophilia-A is an X-linked recessive hereditary disorder characterized by a deficient or defective factor VIII coagulant. It is the most common and most serious hereditary disorder of coagulation. The incidence is one in 5,000 male live births.  Because the intrinsic limb of the coagulation system is disabled, hemostasis depends on vascular and extrinsic mechanisms. As a result, bleeding from the larger rather than the small vessels poses the most serious problem. Furthermore, delayed bleeding is a common phenomenon, occurring after an early period of apparent hemostasis, whereupon an inadequately reinforced clot is unable to maintain vascular integrity. Affected persons have a bleeding tendency that is inversely proportional to the factor VIII levels in the body.
Besides hemorrhage, the patient can give a history of various systemic problems like generalized weakness and orthostatic hypotension; musculoskeletal system symptoms like tingling, cracking, warmth, pain, stiffness and refusal to use joint in children; central nervous system symptoms like one can have headache, stiff neck, vomiting, lethargy, irritability; spinal cord syndromes; gastrointestinal problems like hematemesis, melena, frank red blood per rectum and abdominal pain; involvement of the genitourinary tract leading to hematuria, renal colic and postcircumcision bleeding. Besides these, other problems like epistaxis, oral mucosal hemorrhage, hemoptysis, dyspnea (hematoma leading to airway obstruction), compartment syndrome symptoms and contusions or excessive bleeding with routine dental procedures can occur in hemophilic patients.
A hemophilic patient may have general signs of hemorrhage, like tachycardia, tachypnea, hypotension and orthostatic hypotension. System specific signs of hemorrhage in these patients may be manifested as:
Musculoskeletal system: pain on movement, tenderness, movement range limitation, effusion and warmth in joints.Nervous system: abnormal neurologic findings, altered mental status and meningismus may be found.Gastrointestinal system: hepatic or splenic tenderness and peritoneal signs may be present.Genitourinary system: costovertebral angle pain, bladder spasm, distension and pain may be seen.Other: hematoma leading to location-specific signs, e.g. airway obstruction, compartment syndrome, etc. are likely.
Due to multiple blood transfusions, signs of hepatitis, human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome may be present in these patients.
Our patient did not have the above classical signs and symptoms although he had severe hemophilia, which may be because of regular follow-up and because he was under treatment and better care by parents or because of smaller age. The severity of hemophilia is classified according to the level of clotting factor activity. Factor VIII activity is reported in units, where 1 U/ml corresponds to 100% of factor VIII found in 1 ml of normal plasma. Normal plasma activity usually ranges between 0.5 U/ml and 1.5 U/ml (50-150%).  Severely affected patients have <1% factor VIII activity, while those with moderate disease have 1-4%, and patients with mild disease have 5-50% of normal factor VIII levels. 
Patients with factor VIII <1% of normal are susceptible to spontaneous bleeding resulting in hemarthrosis, soft tissue hematoma and intracranial hemorrhage. Intracranial hemorrhage is common in severe disease and is a significant causes of morbidity and mortality in these patients.  All hemophilia patients, regardless of the severity of the disease, are at risk of excessive bleeding during surgery.  Patients may have low hemoglobin (anemia) due to acute or chronic blood loss in these patients. Large hematomas causes anaemia. There can be an increase in the serum bilirubin due to excessive catabolism of red blood cells.  Diagnosis of hemophilia is often made from family history, laboratory findings such as greatly reduced factor VIII, and elevated aPTT (rest of the investigations like PT, bleeding time, platelet count and clot retraction will be normal) in these patients. 
Correction of the indicated coagulation defect should get priority and must not be delayed, while results of diagnostic tests are awaited 8 . Laboratory studies are usually carried out in hemophilic patients to determine their general condition, management and complications, and their importance is discussed below.
Hemoglobin/hematocrit: to assess blood loss and severity of anemia.PT: tests the extrinsic coagulation pathway. Normal value of PT is expected.aPTT: tests the intrinsic pathway. Elevated values expected may be normal in mild disease.Platelet count: to assess the risk of bleeding; normal range expected.Factor VIII: to assess severity of disease. The normal range is 50-150%, severe <1%, moderate 1-5%, mild disease >5%.Factor VIII inhibitors: to assess the anamnestic response to factor VIII transfusion, factor VII inhibitor is expected to be low titer if the value is 0-10 Bethesda U or high titer if it is >10 Bethesda U.Imaging studies: for timely diagnosis and management of complications of spontaneous bleeding, early and aggressive imaging studies are indicated, even with low suspicion for hemorrhage.  They are helpful in confirmation of bleeding as:
X-ray for assessment of joints is of limited value in acute hemarthrosis. Chronic degenerative joint diseases may however be detected.Head CT scan to assess spontaneous or traumatic hemorrhage, the most severe and deadly complication in these patients.Body CT scan: is performed as and when indicated by clinical suspicion and anatomical location to assess spontaneous or traumatic hemorrhage.Magnetic resonance imaging (MRI): MRI of the head and spine to further assess spontaneous or traumatic hemorrhage.Special studies (as clinically indicated): angiography.Nucleotide bleeding scan: is carried out in rare cases.
In our patient, the aPTT was deranged (increased). All other hematological, biochemical and radiological investigations as regards complications of hemophilia were within the normal limit.
Emergency Care Issue : Treatment of Bleeding in Hemophilia
Hemophilia-associated hemorrhage is preventable if clotting factor replacement therapy is infused to achieve and maintain normal physiologic levels of factor VIII (FVIII) or factor IX (FIX), respectively, for hemophilia A or B. However, such dosing is rarely achieved - essentially only in perioperative hemostatic management - to avoid bleeding following surgery. Therefore, all individuals with hemophilia are at risk for severe bleeding that may quickly evolve to life or limb-threatening circumstances requiring emergency care. 
Emergent bleeding events, while uncommon among people with hemophilia, require recognition and immediate intervention with high-dose clotting factor concentrate (CFC) infusion. Other care, such as surgery, may also be undertaken urgently. However, replacement with FVIII or FIX must occur first or in parallel with any intervention in a patient with hemophilia who is critically ill. Only removal of an acutely injurious agent or cardiopulmonary resuscitation supersedes factor replacement in a critically ill patient with hemophilia. Not only must enough CFC be infused initially to reduce or stop bleeding, it must be also be given as often as necessary to permit healing from the injury. Ideally, measurement of the in vivo factor level on a frequent and ongoing basis is performed to ensure that the desired circulating plasma levels are maintained. Special management considerations relevant to the anatomic bleeding site may exist and contributions from experts in the respective medical field are essential for optimal clinical outcomes. 
High-Risk Hemorrhagic Events that Cause Acute Morbidity or Mortality in Hemophilia -A
These are the guidelines for the management of hemophilia, by World Federation of Hemophilia(WFH), for high risk hemorrhagic events that cause acute morbidity or mortality in hemophilic patients. 
1. Central nervous system hemorrhage
Intracranial hemorrhageSpinal hematoma
2. Soft-tissue hemorrhage predisposing to airway impairment
Retropharyngeal hemorrhage following mandibular molar extraction leading to airway impairment c.f. Ludwig's anginaHemorrhage along facial planesNeck hematoma associated with dissectionTracheal hemorrhage following airway instrumentationLarge tongue hematoma
3. Gastrointestinal bleeding
Hematemesis from esophageal injury or ulceration of gastric or duodenal mucosaHemorrhage from ruptured esophageal varicesHematochezia or melena from bleeding telangiectasia, polyps, etc.
4. Ruptured abdominal organ or capsular hematoma of abdominal viscera
Splenic rupture, kidney capsular rupture, liver lacerationHematoma of bowel wallRuptured appendixRuptured pelvic or abdominal pseudotumor
5. Acute compartment syndrome
Hematoma impingement of nerves and vasculature of extremities
6. Hemorrhage in or around the eye
HyphemaVitreous hemorrhageHematoma following orbital fracture
None of the above high-risk hemorrhagic events were seen till the follow-up of our case, but these are events that always increase the mortality and morbidity in severe hemophilic cases.
Emergency Department Management of Hemophilic Patients
Whenever patients with spontaneous severe bleeding present in the emergency department, the following important things must be followed during management  :
a. Prehospital care
Rapid transport to definitive care is the mainstay.Prehospital care providers should do the following things:
RApply aggressive hemostatic techniques.
Assist patients who are trained for self-administered CFC therapy. Gather focused historical data if the patient is unable to communicate.
b. Emergency department care
Aggressive hemostatic techniques.Coagulopathy must be immediately corrected. Indicated coagulation correction must not be delayed pending diagnostic testing.Diagnostic workup for hemorrhage should be performed.Blood for the diagnostic tests listed above should be drawn, if possible, including two samples to be spun and frozen for factor and inhibitor assays.
Differential diagnoses to be considered when dealing with hemophilic patients are von Willebrand's disease, Vitamin K and other factor deficiencies, afibrinogenemia, dysfibrinogenemia, fibrinolytic defects and platelet disorders.
Basic Principles of Treatment of Bleeding in Hemophilic Patients
These are as per guidelines for the management of hemophilia, by World Federation of Hemophilia(WFH), regarding treatment of bleedings in hemophilic patients. 
Bleeds should be treated with factor replacement therapy at the earliest possible moment, preferably within 2 h of onset of symptoms. Do not wait for the appearance of physical symptomsPatients, even young children, can usually tell when a joint hemorrhage starts. Treatment at this early stage will often stop the bleed before tissue damage occurs. In addition, less factor concentrates will be needed and the patient will recover more quickly.If a person with hemophilia is injured or thinks he may be bleeding, treat him with factor replacement therapy if feasible. "If in doubt, treat"Veins must be treated with care. They are the lifeline for a person with hemophilia. A 23- or 25-gauge butterfly needle is recommended. Never cut down into a vein, except in an emergency, as it destroys the vein. After venipuncture, apply pressure for 3-5 min with one or two fingersAll products that cause platelet dysfunction, especially those containing acetyl salicylic acid (ASA), should be avoided. Use nonsteroidal antiinflammatory drugs (NSAIDs) with caution. Paracetamol/acetaminophen, with or without narcotic analgesics, is usually effective in controlling pain. Avoid intramuscular injections wherever possibleEncourage home therapy with clotting factor concentrates. Home therapy is usually begun when a child is 2-3 years oldCommunication between the patient, his physician, the hemophilia treatment center and the community is essential for optimal management
We followed the above basic principles for control of bleeding in hemophilics while managing the patient.
Guidelines for Acute Management of Severe Hemorrhage in Hemophilia A AND B
All the guidelines given by WHS were kept in mind while managing the patient . ,
Assure adequate airway, breathing and circulation by assessing respiration, pulse and blood pressure (basic cardiopulmonary resuscitation guidelines)Attain venous access as quickly as possibleInfuse appropriate FVIII (hemophilia A) or FIX (hemophilia B) at a dose to achieve physiologic levels immediately (50 IU/kg body weight FVIII or 100-120 IU/kg high-purity FIX, respectively; 70-80 IU/kg of prothrombin complex concentrate if high-purity FIX is unavailable)Obtain CT scan, ultrasound or other imaging studies as indicated to ascertain bleeding site/sourceRequest consultation from appropriate physician consultant for bleeding site (e.g., ophthalmologist for bleeding in/around the eye)HospitalizeMonitor the FVIII/FIX levels respectively on a frequent basis to maintain levels in the mid physiologic rangeContinue with frequent bolus or continuous clotting factor infusions adjusted according to measured FVIII or FIX plasma levels until the acute bleeding event has resolved. Dosing may be adjusted downward as the risk for further bleeding is substantially reducedExamine the patient following hospitalization to manage any sequelae. Ensure appropriate long-term care
Historically, prior to the availability of treatment with factor VIII preparations, most boys died from uncontrolled bleeding, either spontaneous or a bleed after injury, before reaching 20 years of age. Those who survived suffered from the complications of frequent bleeding, primarily severe and incapacitating damage involving their weight-bearing joints. Intracranial hemorrhage occurred with an incidence of approximately one in 200 per year, often with severe permanent brain damage in survivors of the initial bleeding episode.
For severe hemophilia-A, current optimal treatment should have two goals. The first is to provide sufficient factor VIII to prevent spontaneous bleeding. The second is to provide sufficient factor VIII to have normal coagulation function after any trauma.  The therapeutic goal is to achieve a clinical situation that is roughly similar to individuals with moderate hemophilia-A in whom the concentration of factor VIII activity is more than 2% by standard clotting assays. , At the present time, the optimal treatment so defined requires much medical and family support, primarily due to the relatively short half-life of infused factor VIII (approximately 10 h).
Factor VIII requires intravenous infusion and is rapidly bound to its carrier molecule von Willebrand protein. Without effective interaction with the von Willebrand protein, the infused factor VIII disappears rapidly (in minutes) due to degradation by plasma proteases, as occurs in the subtype of von Willebrand disease, Type N (for Normandy, where it was first described), in which the protein domain of von Willebrand protein that interacts with factor VIII is rendered ineffective by mutations. Two major concerns continue to trouble current optimal treatment approaches: some patients will develop neutralizing antibodies during the first 50 infusions of therapeutic factor VIII and, second, to administer therapeutic factor VIII every other day in young boys often requires placement of a central venous access device, and such use carries the life-threatening risks of infection and thrombosis. 
While preparing these patients for surgery, levels of factor VIII are routinely raised toward around 100% of normal activity, which should be maintained for the first three postoperative days. From the fourth day onwards, these levels should be maintained at around 80%, and it is allowed to decline to 40% of normal activity from the 7 th day onwards. The formula used to calculate the factor VIII dose is, N = plasma volume (ml/kg) ΄ weight (kg) ΄ percent activity increase, where N is the number of units required. The plasma volume is 40 ml/kg for adults.  As the half-life of factor VIII is about 12 h, it must be administered twice daily. Therefore, we transfuse it 2 h before and 6 h after the surgery. Cryoprecipitate is the next choice of blood product in the management of hemophilia-A, which provides 80 units of factor VIII per bag. But, as cryoprecipitate contains fibrinogen, serum levels of fibrinogen may rise and increase the risk of bleeding in spite of normal amounts of factor VIII if excessively transfused. 
Our decision to proceed with general anesthesia was based on the need for complete relaxation of the child while removing the FB to avoid surgical trauma and to secure the airway to avoid aspiration from intraoral bleeding. Meticulous care has to be taken in manipulation or intubation of the airway as it can cause submucosal hemorrhage, which may become life threatening. Nasal intubation should be avoided as it can prove traumatic, and bleeding from the site can lead to aspiration. Care should be taken during positioning of the extremities, which must be done gently, avoiding excessive force, to prevent development of hemarthrosis. Analgesics such as aspirin and other NSAIDs for postoperative pain relief may predispose to gastrointestinal hemorrhage. Intravenous analgesics including narcotics offer good pain relief. Patient-controlled analgesia is a safe and effective alternative, although it may be difficult to use in very young children. An intramuscular injection of analgesics is a poor choice in hemophilics because of the risk of hematoma, and this should be avoided. Fibrinolytic inhibitors, epsilon amino-caproic acid (EACA) or tranexamic acid are commonly administered to reduce the requirement of factor VIII. Vasopressin analogue DDAVP (Desamino-VIII-Darginine vasopressin), which increases the plasma concentration of factor VIII, can be administered intravenously. 
A review of the recent literature for the management of hemophilic patients focuses on some important information. To assess the effect of factor VIII level on breakthrough bleeding rates in patients with severe hemophilia-A on prophylaxis, data demonstrate that increasing time with a FVIII below 1 IU/dL is associated with increased total bleeds and hemarthrosis. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance. 
Pediatric patients with hemophilia and inhibitors are at particular risk of recurrent hemarthrosis. Management of these patients should seek to avoid joint damage and support the child's full social and physical development. Current options for management of bleeding complications include on-demand treatment of acute bleeding episodes, secondary prophylaxis to avoid recurrent bleeds and surgery to treat affected joints. There is a rationale for adopting prophylactic approaches to prevent bleeding in inhibitor patients, allowing these groups similar opportunities for protection against arthropathy development, as are given to noninhibitor patients. 
An important management issue with these patients has been the development of endogenous FVIII inhibitors, which may render traditional therapy ineffective. Patients are usually either "low responders" or "high responders" with regard to FVIII inhibitor production. Treatment options for patients with inhibitors include replacement therapy with porcine FVIII, plasmapheresis, prothrombin complex concentrate administration and recombinant FVIIa therapy. , Responses from 42 centers dealing with 2,642 children <18 years with severe hemophilia show that, in addition to genetic factors, early intensive treatment was considered important for inhibitor development. Other factors likely to reduce inhibitor development were early onset of prophylaxis and avoidance of early surgery.  One trial compared prophylactic infusions in young children to prevent any spontaneous bleeding versus on-demand treatment with infusions of recombinant factor VIII. The regular prophylactic infusion schedule led to reduced spontaneous bleeding and much less joint damage,  but commercially produced factor VIII can be a vector for transmission of hepatitis A and HIV.
Approximately 5-8% of severe hemophilia patients are treated with NovoSeven; (Novo - Norkisk Company). It is a preparation of activated factor VII, and/or FEIBA (factor VIII inhibitor bypassing activity), a plasma-derived preparation of coagulation factors that has been partially activated during the preparation process.  In one recent approach, the recombinant factor VIII molecule is noncovalently attached to a pegylated liposome molecule prior to infusion. In two phase-I clinical trials, this preparation was shown to be safe for at least one infusion in patients with severe hemophilia-A and to prolong the interval free of spontaneous bleeding after the prophylactic infusion. 
We followed the guidelines regarding management during major and minor surgery in the hemophilic patients to get optimal outcome, decreasing the chances of profuse bleeding.
Guidelines Regarding Management During Major and Minor Surgery
These are the guidelines for the management of hemophilia, by World Federation of Hemophilia(WFH), during major and minor surgery in hemophilic patients. 
A surgical patient is best managed at a hemophilia treatment center. The center where the surgery is to be performed must be capable of performing a factor inhibitor screen and measurement of serial factor levelsOnce the coagulation defect is corrected, operative and invasive procedures can be performed. A consultation with a hematologist is necessaryDocument the patient's individual response to the replacement therapy prior to surgery. Rule out an inhibitor if the patient does not respond adequatelyImmediately prior to the procedure, the factor level must be raised to the appropriate level required for hemostasisAn appropriate factor level should be maintained for 5-7 days or until wound healing after minor surgery, and for 10-14 days after major surgery (vide supra). After some orthopedic procedures, factor level maintenance may be needed for a longer periodDuring minor invasive procedures:
Infuse factor concentrates before invasive diagnostic procedures are performed. These procedures include lumbar puncture, arterial blood gas determination, bronchoscopy with brushings or biopsy and gastrointestinal endoscopy with biopsy.Allergic reactions to factor replacement products: use the filters included in factor packages to avoid the possibility of reaction.To prevent or reduce symptoms, use antihistamines.Changing the brand of clotting factor concentrate sometimes reduces symptoms.
Other approaches not yet in clinical trial include genetic modifications of factor VIII to extend the half-life after infusion, to use gene therapy approaches to express normal factor VIII and genetic modifications to extend the half-life of factor VII to allow effective coagulation in the absence of normal factor VIII.  Previous studies have focused on preventing joint damage. The new paradigm is to prevent any spontaneous bleeding at all. Fibrogammin (R) P is a purified, pasteurized concentrate of FXIII that appears to carry a negligible risk of viral transmission, unlike other unprocessed products containing FXIII. An ongoing phase II/III study of fibrogammin (R) P in patients with congenital FXIII deficiency is being conducted to evaluate the prophylactic efficacy and long-term safety of this product. Patients reported no severe spontaneous bleeds during fibrogammin (R) P therapy.  The another area for consideration reflects that for the past two decades, the hemophilia community has pushed diligently for factor VIII that was safer, with safety defined as higher purity factor VIII protein with no associated human plasma-derived products.
Successful management of hemophilic patients can be done as in our case. One should follow the general principles of management of bleeding and specific guidelines of WFH for acute severe hemorrhage and emergency care issues' while managing complications of bleeding in the emergency department. Multidisciplinary planning, coordination of care, recent treatment options and timely communication is crucial in ensuring a successful outcome while managing patients with rare, congenital and severe bleeding diatheses, e.g. hemophilia-A. Whenever symptomatology suggests the possibility of this disorder, the diagnosis needs to be confirmed by laboratory testing, including FVIII level, to assess severity of the disease and the presence of any FVIII inhibitor. Prompt action should be taken for general problems before the onset of life-threatening complications during management. Recent treatment options for general care, bleeding complications and inhibitors promise good results. Multicentric trials with recently available liposomal FVIII, fibrogammin (R) P, highly purified FVIII and gene therapy are needed for best outcome and longer life of the hemophilic population.
|1||Dhar P, S. Abramovitz S, DiMichele D, Gibb CB, Gadalla F. Management of pregnancy in a patient with severe hemophilia A. Br J Anaesth 2003;91:432-5.|
|2||MacKinlay N, Taper J, Renisson F, Richard K. Cardiac surgery and catheterisation in patients with hemophilia. Haemophilia 2000;6:84-8.|
|3||Martinowitz U, Batorova A. Continuous infusion of coagulation products in hemophilia. Textbook of Hemophilia. Oxford and New York: Blackwell Science 2005. p.; 46-52.|
|4||Cahill MR, Colvin BT. Hemophilia. Postgrad Med J 1997;73:201-6|
|5||Dietrich S. Treatment of Hemophilia Bleeding with Limited Resources, Treatment of Hemophilia Monograph #1, Montreal,Canada: WFH, 1996, revised 2004. Available from: http://www.wfh.org |
|6||Scharf R, Kucharski W, Nowak T. Surgery in hemophilia A patients with factor VIII inhibitor: 10-year experience. World J Surg 1996;20:1171-- 81.|
|7||Mannucci PM. Back to the future: a recent history of hemophilia treatment. Haemophilia 2008;14:10-8.|
|8||Kitchen S, McCraw A. For the WFH Laboratory Sciences Committee. Diagnosis of Hemophilia and Other Bleeding Disorders. Montreal, Canada: WFH. Available from: http://www.wfh.org |
|9||Hoots WK. Emergency care issues in hemophilia. Treatment of hemophilia. World Federation of Hemophilia. Vol-43. Available from: http://www.wfh.org |
|10||World Federation of Hemophilia. Guidelines for the Management of Hemophilia, Montreal, Canada: WFH; Available from: http://www.wfh.org |
|11||World Federation of Hemophilia. Hemophilia in Pictures: WFH. Available from: http://www.wfh.org [last cited in 2005]|
|12||Chandy M. Treatment options in the management of hemophilia in developing countries. World Federation of Hemophilia. Vol-37. Available from: www.wfh.org |
|13||Ljung RC. Intracranial hemorrhage in hemophilia A and B. Br J Haematol 2008;140:378-84.|
|14||Darby SC, Kan SW, Spooner RJ, Giangrande PL, Hill FG, Hay CR, et al. Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV. Blood 2007;110:815-25.|
|15||Jayandharan GR, Srivastava A. The phenotypic heterogeneity of severe hemophilia. Semin Thromb Hemost 2008;34:128-41.|
|16||Neunert CE, Miller KL, Journeycake JM, Buchanan GR. Implantable central venous access device procedures in hemophilia patients without an inhibitor: systematic review of the literature and institutional experience. Haemophilia 2008;14:260-70. |
|17||De Gruchy"s. Clinical haematology in medical practice, Coagulation disorders. Oxford: Oxford University Press; 1993. p. 406-36.|
|18||Collins PW, Blanchette VS, Fischer K, Bjorkman S, Oh M, Fritsch S, et al. Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A. J Thromb Haemost 2009;7:413-20. |
|19||Chuansumrit A, Treepongkaruna S, Phuapradit P. Combined fresh frozen plasma with recombinant factor VIIa in restoring hemostasis for invasive procedures in children with liver diseases. Thromb Haemost 2001;85:748-9 |
|20||Kenet G, Lubetsky A, Gitel S, Luboshitz J, Varon D, Martinowitz U. Treatment of bleeding episodes in patients with hemophilia and an inhibitor: comparison of two reatment protocols with recombinant activated factor VII. Blood Coagul Fibrinolysis 2000;11:S35-8.|
|21||Santagostino E, Morfini M, Auerswald GK, Benson GM, Salek SZ, Lambert T, et al. Paediatric hemophilia with inhibitors: existing management options, treatment gaps and unmet needs. Haemophilia 2009;15:983-9.|
|22||Van den Berg HM, Chalmers EA. Clinical prediction models for inhibitor development in severe hemophilia A. J Thromb Haemost 2009;7:98-102.|
|23||Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007;357:535-44.|
|24||Jiménez-Yuste V, Alvarez MT, Martín-Salces M, Quintana M, Rodriguez-Merchan C, Lopez-Cabarcos C, et al. Prophylaxis in 10 patients with severe haemophilia A and inhibitor: different approaches for different clinical situations. Haemophilia 2009;15:203-9. |
|25||Spira J, Plyushch OP, Andreeva TA, Khametova RN. Evaluation of liposomal dose in recombinant factor VIII reconstituted with pegylated liposomes for the treatment of patients with severe hemophilia A. Thromb Haemost 2008;100:429-34.|
|26||Kasuda S, Kubo A, Sakurai Y, Irion S, Ohashi K, Tatsumi K, et al. Establishment of embryonic stem cells secreting human factor VIII for cell-based treatment of hemophilia A. J Thromb Haemost 2008;6:1352-9.|
|27||Lusher J, Pipe SW, Alexander S, Nugent D. Prophylactic therapy with Fibrogammin(R)P is associated with a decreased incidence of bleeding episodes: A retrospective study. Haemophilia 2009.In press.|