Haem Pres 2012 Stef.docx

Patient’s Demographics Gender: Male Age: 15 years

Presenting Complaint The patient presented with a two day history of a swollen left knee. There is no history of trauma but he has had a history of repeated swellings of the same knee, the other knee and elbows from childhood for which he has been seen and treated for at the hospital.

Comments on the history The patient is a 15 year old male and he has symptoms of recurrent swollen joints. Swollen joints happen when there's an increase of fluid in the tissues that surround the joints. Swellings can be due to haemarthrosis, gout or septic arthritis. Given the patient’s age of 15 years the swelling is most likely due to haemarthrosis. Haemarthrosis is the accumulation of blood in a joint or its synovial cavity. It can happen due to injury, patients on anticoagulants or those who have haemophilia. From his history he had not experienced any trauma nor was he or any medication therefore it can be said that haemarthrosis on this patient was due to haemophilia. Also haemophilia is a recessive sex linked, X chromosome disorder so this happens more likely in males than females. Questions about excessive bleeding after dental extractions if he had any as well as spontaneous haematuria could have also been asked. With haemophilia other physical findings could be large bruises on falling or excessive physical activity, joint deformity and haematomas. Usually this occurs with fever, skin discoloration, and pain.

Comments on laboratory results A CBC was done, together with Prothrombin time (PT), Activated Partial Thromboplastin Time (APTT). Below is a table showing the components measured, the patient’s values and their corresponding normal ranges. Components Hb MCV WCC Platelets PT APTT



 







Patient’s results 10g/dl 80 fl 8x10^9/l 200x10^9/l 13 s 91 s

Normal Ranges 14-18g/dl 78-98fl 4.1-10.9x10^9/l 150-400x10^9/l 12 s 30 s

Haemoglobin is decreased which suggests that there may be internal bleeding occurring in the joint of the left swollen knee of this patient as there is no evidence of external trauma in this patient. The Mean Corpuscular Volume is within normal range, which shows that there is no change in the average red blood cell size. White cell count is within normal range, which indicates there is not any infection or inflammatory process present in his left knee. This could rule out septic arthritis being a cause of his swelling as well. Platelets are within the normal range. Blood clotting is impaired in haemophilia, therefore they are not being consumed in the clotting process. PT measures the integrity of the extrinsic coagulation pathway (prothrombin,fibrinogen, V, VIII,X). The PT is prolonged with abnormalities in these factors , liver disease or if the patient is on warfarin. The patient’s PT was normal in this case. APTT measures the integrity of the intrinsic coagulation pathway (XII, XI, IX, VIII, X, V, II or I (but not factor VII)). The patient’s APTT was prolonged due to a deficiency in factor VIII or factor IX which causes either Haemophilia A or B respectively.

The main laboratory features of haemophilia A are shown in Table 1. The abnormal findings are a prolonged APTT and a reduced level of factor VIII. The PT, bleeding time and vWF level are normal.

Bleeding Time PT APTT VIII vWF

Normal Normal ↑+ ↓++ Normal

TABLE 1 : BLOOD CHANGES IN HAEMOPHILIA A

Investigations to confirm Diagnosis The inheritance and clinical features of factor IX deficiency(Christmas disease, Haemophilia B) are identical to those of Haemophilia A. The two disorders can only be distinguished by specific coagulation factor assays. The incidence of Haemophilia B is one-fifth that of Haemophilia A(30-100 per million population) Firstly a correction mix 50:50 is performed by adding normal plasma with the patient’s plasma to see if the APTT value normalizes. If it normalizes then a blood sample should be taken and the amount of factor VIII and IX should be measured in the blood. Factor VIII is the protein which is lacking in Haemophilia A and factor IX is the protein which is lacking in Haemophilia B. Factor VIII is also known as anti-hemophilic factor (AHF) and is a cofactor for IXa. In the presence of Ca2+ and phospholipids, a complex is formed that activates factor X into Xa. It is also protected by Von Willebran factor by forming a stable complex with it. Since this is so a factor VIII- VWF binding assay and a VWF antigen assay should be done. Von Willebran is sometimes mistake for haemophila but this disease is more common in females and there is mucous membrane bleeding , excessive blood loss from superficial

cuts and abrasions , haemarthroses and muscle haematomas are rare in this case. Haemophila may also be confused with severe Vitamin K deficiency. This deficiency can be diagnosed with a prolonged PT test. However, since the PT result was found to be normal this disorder can be ruled out. DNA studies can also be performed to detect the type of haemophilia. Imaging studies can also be done to aid in diagnosis.X-ray can be done to examine joints for bone deformities and damage. Head CT scans without contrast are used to assess for spontaneous or traumatic intracranial haemorrhage.MRI on the head and spinal column for further assessment of spontaneous or traumatic haemorrhage is also useful in the evaluation of the cartilage, synovium, and joint space. Ultrasonography is useful in the evaluation of joints affected by acute or chronic effusions. This technique is not helpful for evaluating the bone or cartilage.

Diagnosis The patient has either Haemophilia A or B and is experiencing haemarthroses in his left knee. The history together with the test’s results indicates this. The type of Haemophilia would be ascertained during further investigations as described above. The patient’s condition can be classified as an inherited coagulation protein disorder since he has been experiencing these symptoms since childhood and his platelet numbers are normal but he has an increased APTT value.

Management Physical examination of patient should be done to assess sites of bleeding whether it is haemarthroses, muscle, intracranial, airway or retroperitoneal. When the type of haemophilia has been confirmed that patient should be administered that factor that is deficient. A portacath would be needed to deliver the factor concentrate in order to treat the bleeding. If the patient has haemophilia A then: Dose VIII = % increase VIII x wt(kg)/2 • T1/2 VIII = 8-12 hours • Haemarthrosis : 25%

• Muscle : 50% • Intracranial, airway, retroperitoneal : 100% then 50% for 7-10 days Factor VIII has a half-life of 12 hours and therefore must be administered at least twice daily to maintain the required therapeutic level .Recombinant factor VIII concentrate can be used if available to minimize side effects. Synthetic vasopressin (Desmopressin - an analogue of vasopressin) intravenous, subcutaneous or intranasal – can be administered it produces a rise in factor VIII proportional to the initial level of factor VIII and avoids the complications associated with blood . Cryoprecipitate may be used if F VIII concentrates are unavailable since it contains F VIII, fibrinogen and vWF. Fresh frozen plasma can also be used to stop the bleeding and regulate the APTT in both Haemophilia A and B. Antifibrinolytic agents can be used in long term management to treat mild bleeding. These agents are used in addition to F VIII or F IX replacement for oral mucosal haemorrhage and prophylaxis, as the oral mucosa is rich in native fibrinolytic activity. Their use is contraindicated as initial therapies for haemophilia-related haematuria originating from the upper urinary tract because they can cause obstructive uropathy or anuria. Prophylactic treatment. The main goal of prophylactic treatment is to prevent bleeding symptoms and organ damage, in particular to joints. At the first spontaneous joint bleed, most boys with severe haemophilia A are started on prophylactic F VIII three times a week. The aim is to keep the F VIII level above 1% to avoid serious complications. Prophylactic treatment can also be used in F IX deficiency. This treatment is given using a port-a-cath but it is very expensive. Adjunctive Therapy: The patient should be advised that he should remain immobilized (bed rest) so as to prevent possible injury and subsequent bleeds which can be incurred if he walks into any structures. The acronym RICE (rest, ice, compression and elevation) can be applied to help manage the patient’s haemarthroses. Aspirin, anti-platelet drugs and IM injections should be avoided to prevent further bleeding. Hence non- aspirin analgesics can be administered to relieve pain. Patient is advised to refrain from intense

physical activity and to stay away from sharp objects to reduce risk of injury. Specific to this patient: This patient has a major haemorrhage there he should be treated with recombinant F VIII for Haemophilia A and F IX for Haemophilia B to maintain the respective factor levels at 50% of normal. This patient can avoid bleeding episodes by undergoing prophylactic treatment. The patient should be started on prophylactic F VIII/IX three times a week with the aim of keeping his F VIII/IX above 1%.

Pathogenesis of Haemophilia. There are two main types of haemophilia; haemophilia A and haemophilia B. Haemophilia C also exits . In haemophilia A, the level of factor VIII is reduced. Factor VIII is a cofactor for the intrinsic pathway and is synthesized by the reticuloendothelial cells of the liver. It also has procoagulant properties. The prevalence of haemophilia A is about 1 in 5000 of the male population. It is inherited as an X-linked disorder. If a female carrier has a son, he has a 50% chance of having haemophilia, and a daughter has a 50% chance of being a carrier (FIGURE 1). All daughters of men with haemophilia are carriers and the sons are normal. The human factor VIII gene is vast, constituting about 0.1% of the X chromosome, encompassing 186 kilobases of DNA. Various genetic defects have been found, including deletions, duplications, frame shift mutations and insertions. In approximately 50% of families with severe disease, the defect is an inversion. There is a high mutation rate, with one-third of cases being apparently sporadic with no family history of haemophilia.

FIGURE 1 : INHERITANCE PATTERN OF HAEMOPHILIA

Haemophilia B is an inherited X liked recessive disorder resulting in factor IX deficiency and clinical symptoms are identical to those of haemophilia A. Indeed, the two disorders can only be distinguished by specific coagulation factor assays. The incidence is one-fifth that of haemophilia A. Factor IX is coded by a gene close to the gene for factor VIII near the tip of the long arm of the X chromosome. Its synthesis, like that of prothrombin, factor VII, factor Xand protein C, is vitamin K-dependent. Carrier detection and antenatal diagnosis is performed as for haemophilia.

Classification of Haemophilia Table showing the level of coagulation factor activity correlates with the disease. Severe

Factor VIII activity <1%

Moderate

1-5%

Mild

5-20%

Clinical Features Frequent spontaneous bleeding Joint deformities if not treated Post traumatic bleeding Occasional Spontaneous bleeding Post traumatic bleeding

The most common causes of death in people with haemophilia are cancer and heart disease, as for the general population. Cerebral haemorrhage is much more frequent however, and in recent years, HIV infection and liver disease (due to hepatitis C) have become a more common cause of death.

Blood Product of Choice: When further tests are done and if the patient is confirmed with either Haemophilia A/B factor VIII/IX can be used respectively. Cryoprecipitate is most appropriate to treat this patient. It contains factor VIII,VWF and fibrinogen. The dosage is 1 unit/ kg.

Instructions to nurse:    

 

 



Check patient’s vitals which include blood pressure, heart rate, pulse and respiratory rate before the transfusion. Before starting the transfusion please ensure that the patient’s name and the name on the blood bag are the same. Check to ensure the patient is receiving the correct amount of units of product required. When establishing an IV line be sure it is flushed with 0.9% saline solution before the pack is opened. Please use a portacath for transfusion since patient is a haemophiliac and we want to reduce the risk of any bleeds. Check the expiry date on the bag and for any damage to the pack. Start transfusion within 30 minutes of the cryoprecipitate leaving the blood bank, but ensure that the it is at the right temperature (37 degrees Celsius) before administration. Check patient vitals every 15 minutes for the first hour of transfusion and then hourly until the transfusion is finished. If any major reactions may occur please stop the transfusion immediately and record it and administer piriton. Notify blood bank of any reactions so they can verify that the correct blood pack was give. Symptoms to look out for during the transfusion: An increase in temperature may indicate a fever, dyspnoea, an allergic reaction (itchy



skin, rashes on the skin, runny nose, swelling under the skin, headache, flushing, vomiting, hypotension. When transfusion is finished do not discharge patient until they are well enough to do so i.e. keep them for observation to ensure that their vitals are stable and there are no delayed reactions.

Possible side effects of transfusions: Multiple side effects can occur during or after the administration of blood components. In this case cryoprecipitate is used. It is obtained by thawing FFP at 40C.There are immunological reactions that can be divided into Immediate and Delayed complications, as well as Haematological complications also divided into Immediate and Delayed. Besides these complications, there is always the potential of human blood products to transmit infectious agents, because of viral, bacterial, or prior contamination. Transfusions also carry the risks of circulatory overload, or metabolic complications. Immediate immunological complications: 1) Febrile non-haemolytic allergic reactions: caused by hypersensitivity to donor plasma proteins and can possibly lead to anaphylactic shock. The clinical features are urticaria, pyrexia and in severe cases, dyspnoea, facial oedema and rigors. Immediate treatment is with antihistamines and hydrocortisone or adrenaline. Washed red cells or frozen red cells may be needed for further transfusions if the majority of plasma-removed blood causes reactions. 2) Allergic reaction: Seen in approximately 1% of recipients and caused by foreign plasma proteins. On rare occasions they may be associated with laryngeal oedema and bronchospasm. If urticaria occurs in isolation (without fever and other signs), slow the rate or temporarily stop transfusion. If symptoms are bothersome, consider administering an antihistamine before restarting the transfusion. If associated with other symptoms, cease the transfusion and proceed with investigation. 3) Anaphylactic reactions: Anaphylactic and anaphylactoid reactions have signs of cardiovascular instability including hypotension, tachycardia, loss of consciousness, cardiac arrhythmia, shock and cardiac arrest. Sometimes respiratory involvement with dyspnoea and stridor are prominent. In some cases patients with IgA deficiency who have anti-IgA antibodies can have these reactions. Immediately stop transfusion, supportive care including

airway management may be required. Adrenaline may be indicated. Usually given as 1:1000 solution, 0.01mg/kg s.c./i.m. or slow i.v. Patients with anti-IgA antibodies require special blood products such as washed red blood cells and plasma products prepared from IgA deficient donors. Manage further transfusion in consultation with the haematologist-on-call. 4) Transfusion-related acute lung injury (TRALI): This presents within 6nhours of an infusion as pulmonary infiltrates with chest symptoms depending on the severity. It is caused by positive transfer of HLA antibodies in donor plasma causing endothelial and epithelial injury. Most of the donors are multiparous women. Management is supportive. 5) Acute transfusion reaction: The majority of haemolytic reactions are caused by transfusion of ABO incompatible blood. Most haemolytic reactions are the result of human error such as the transfusion of properly labelled blood to the wrong patient, or improper identification of pretransfusion blood samples. Non-immune haemolysis of RBCs in the blood container or during administration can occur due to physical disruption (temperature changes, mechanical forces, non-isotonic fluid)Chills, fever, pain (along IV line, back, chest), hypotension, dark urine, uncontrolled bleeding due to DIC.Immediately stop transfusion. Notify hospital blood bank urgently (another patient may also have been given the wrong blood!). These patients usually require ICU support and therapy includes vigorous treatment of hypotension and maintenance of renal blood flow.Proper identification of the patient from sample collection through to blood administration, proper labelling of samples and products is essential.

Delayed immunological complications: 1) Alloimmunization: Antigens on transfused cells may cause alloimmunization of the recipient who may experience antibody reactions to subsequent transfusions. Sometimes a patient who has received many blood product transfusions develops antibodies against parts of the red blood cells or platelets in a donated unit of blood. It does not always cause any symptoms. Alloimmunization can be prevented by giving patients red blood cells that do not have the antigens that the patient’s antibodies attacked or by filtering white blood cells out of the blood product. Tests should be done before future transfusions to check for possible immune responses.

2) Graft-versus-host disease (GVHD): this may occur when lymphocytes are transfused to an immunocompromised patient. Symptom are fever, liver problems, diarrhea and rashes. It is prevented by irradiation of blood product. It is almost uniformly fatal.

Immediate haematological complications: 1) Haemolytic transfusion reactions: can be immediate or delayed. Immediate life-threatening reactions associated with massive intravascular haemolysis as a result of complement-activating antibodies of IgM associated with the ABO system. Delayed haematological complication: 1) Delayed haemolytic transfusion reaction: Symptoms appear within 1-4 weeks. Patient may be asymptomatic or have a slight fever. The first clue is an unexpected drop in HCT. It is managed in a similar manner as acute transfusion reaction which includes stopping the transfusion while keeping the IV line open and flushing it with 0.9% saline and furosemide. Hydrocortisone (100mg IV) and antihistamine will help alleviate shock. Contact laboratory to check for any errors in compatibility testing or labeling of bag. Repeat cross match and check patient for haemoglobinuria. Transfuse patient with a different blood pack. Non-haemolytic, non-immunologic complications 1) Transmission of infectious disease may occur because this product is made from human blood. This may be due to known or unknown agents, such as viruses. This may occur despite careful selection of donors and testing of blood. Donor selection criteria are designed to screen out potential donors with increased risk of infection with HIV, HTLV, hepatitis, and syphilis, as well as other agents. Transmission of CMV by transfusion may be of concern in low-birth weight (≤1200 grams) premature infants born to CMV seronegative mothers and in certain other categories of immunocompromised individuals, if they are CMV seronegative. For at-risk recipients, the risk of CMV transmission by cellular components can be reduced by transfusing CMV seronegative or leukocyte-reduced components.

2) Bacterial contamination occurs rarely but can cause acute, severe, sometimes life-threatening effects. Onset of high fever (≥2 0C rise in temperature), severe chills, hypotension, or circulatory collapse during or immediately after transfusion should suggest the possibility of bacterial contamination and/or endotoxin reaction. 3) Volume overload: This is due to the increase in plasma volume after transfusion. It is managed through the use of a diuretic and can be prevented by slow transfusion of the required products. 4) Citrate toxicity: Citrate is the anticoagulant used in blood products. Rapid administration of large quantities of stored blood may cause hypocalcaemia and hypomagnesaemia when citrate binds calcium and magnesium. This may result in myocardial depression. Management includes slowing of transfusion or temporarily stopping it so that the citrate can be metabolised. Replacement therapy may also be necessary for those with symptomatic hypocalcaemia and hypomagnesaemia.