MANAGEMENT OF WARFARIN OVERDOSE AND REVERSAL

Introduction

Bleeding while on oral anticoagulants increases significantly with INR results >5.0. Therapeutic decisions are dependant on the INR and whether there is minor or major bleeding. The dose of vitamin K used to reverse over anticoagulation depends on the INR. ...In the presence of major bleeding it is recommended that intravenous (IV) vitamin K is used. The dose will depend on whether partial or complete reversal is required.

A dose of 1-2mg /IV will partially correct the INR to a level of 2-3 and anticoagulation can be continued. For complete reversal 5-10mg/IV is recommended and this may have a sustained effect, delaying successful re-anticoagulation with warfarin.

Given at a rate of less than 1mg/minute reactions to this preparation are rare.

Oral vitamin K can be used if reversal is non-urgent. The oral dose for partial reversal is 0.5-2.5mg.If the INR is still too high at 24h the dose of vitamin K can be repeated.

Bleeding may occur when patients are not over-anticoagulated. In these circumstances, it may still be necessary to reverse anticoagulation and identify the cause of bleeding. In patients with mechanical heart valves it is recommended that IV heparin is recommenced once bleeding has stopped and the problem identified.

Unexpected bleeding at therapeutic levels: investigate for possible cause e.g. alimentary or renal disease(ca-bladder or large bowel). - Seek advice from a Haematologist.

FFP contains insufficient concentration of the vitamin K factors - especially factor IX to reverse warfarin, supporting the finding that FFP is not the optimal treatment. FFP(15ml/kg) is only recommended if there is major bleeding in a patient. Prothrombin Complex Concentrate (PCC) preparations are more rapid and complete in their reversal effect. PCC (trade name Octaplex) is indicated for reversal of warfarin effect during major bleeds and intracerebral haemorrhage. The BCSH guidelines on Oral Anticoagulation recommend prothrombin complex concentrate as an alternative to FFP,when major bleeding complicates anti-coagulant overdose. Contact a Haematologist to request this product.Recommendations for management of bleeding and excessive anticoagulation:

Excessive anticoagulation:

INR between 3.0 - 6.0 (target INR 2.5) INR between 4.0 - 6.0 (target INR 3.5) Action: -Reduce warfarin or stop -restart when INR <5.0

INR between 6.0 - 8.0 no bleeding or minor bleeding Action: -Stop warfarin

-restart when INR <5.0

INR >8.0 no bleeding or minor bleeding Action: Stop warfarin restart when INR <5.0 If other risk factors for bleeding give 0.52.5 mg of vitamin K (oral) or 1-2mg IV

Major bleeding i.e. > 30% blood volume (1500-2000ml) in adult Action: Stop warfarin -Contact Haematologist -Give prothrombin complex concentrate (Octaplex) or FFP 15 ml/kg -Give 5-10 mg of vitamin K (IV) -Repeat coagulation tests post infusion after 4 Hours.

Intracranial haemorrhage.

- Contact Haematologist -Give prothrombin complex concentrate

(Octaplex) and 5mg vitamin K IV. -Repeat coagulation tests post infusion and at 12 and 24 hours.

Octaplex Prothrombin Complex Dosage:

The dose of Octaplex PCC will depend on the INR before treatment and the targeted INR. -In the following table approximate doses (ml/kg body weight of the Reconstituted product) required for normalisation of INR ( 1.2 within 1 hour) at different initial INR levels are given.

*Initial INR: 2.0 2.5

Approximate Dose:( 0.9-1.3ml Octaplex/kg).

*Initial INR: 2.5- 3.0

Approximate Dose: ( 1.3 1.6 ml Octaplex/kg).

*Initial INR: 3.0 3.5

Approximate Dose: ( 1.6 1.9 ml Octaplex/kg).

*Initial INR: > 3.5

Approximate Dose: ( > 1.9 ml Octaplex/kg).

*The single dose should not exceed 120ml Octaplex (3,000 IU).

-The use of PCCs carries a risk of thrombosis and should be reserved for life threatening situations such as severe haemorrhage and haemorrhage into vital organs .e.g intracranial haemorrhage. Severe haemorrhage is defined as ableeding which poses genuine risk to life, limb, sight or brain. Bleeding should always be considered in patients on anticoagulants with Severe headache even when INR is in the therapeutic range. It is essential that intravenous (IV) vitamin K is given at the same time as a PCC in order to switch on endogenous synthesis of vitamin K dependent clotting factors. It is now clear that oral vitamin K has no therapeutic usefulness in clinical settings that require rapid warfarin reversal because it works too slowly. Note: The correction of the INR persists for approximately 6-8 hours. Hence it Is vital to administer vitamin K along with Octaplex PCC if a sustained effect is desirable. The effects of vitamin K, if administered simultaneously, are usually achieved Within 4-6 hours, thus the effect of vitamin K should be evident before the effect of the PCC wears off.

Instructions for use/handling of Octaplex: Please read all the instructions and follow them carefully. During the procedure described below, aseptic technique must be maintained. The product reconstitutes quickly at room temperature to a clear or slightly o Opalescent solution. Do not use solutions that are cloudy or have deposits. After reconstitution, the solution must be used immediately. It is recommended to use the transfer set included in the package. Instructions for Reconstitution:

1. Warm the solvent (Water for Injections) and the concentrate in the closed vials up to room temperature. This temperature should be maintained during reconstitution. 2. Remove the caps from the concentrate vial and the water vial and clean the rubber stoppers with an alcohol swab. 3. Remove the protective cover from the short end of the double-ended needle,making sure not to touch the exposed tip of the needle. Then perforate the centre of the water vial rubber stopper with the vertically held needle. In order to withdraw the fluid from the water vial completely, the needle must be introduced into the rubber stopper in such a way that it just penetrates the stopper and is visible in the vial. 4. Remove the protective cover from the other, long end of the double-ended needle, making sure not to touch the exposed tip of the needle. Hold the water vial upside-down above the upright concentrate vial and quickly perforate the centre of the concentrate vial rubber stopper with the needle. The vacuum inside the concentrate vial draws in the water. 5. Remove the double-ended needle with the empty water vial from the concentrate vial, then slowly rotate the concentrate vial until the concentrate is completely dissolved. Octaplex dissolves quickly at room temperature to a colourless to slightly blue solution. 6. Reconstituted products should be inspected visually for particulate matter and discoloration prior to administration. If the concentrate fails to dissolve completely or an aggregate is formed, do not use the preparation. Instructions for Injection: 1. After the concentrate has been reconstituted in the manner described above,remove the protective cover from the filter needle and perforate the rubber stopper of the concentrate vial.

2. Remove the cap of the filter needle and attach a 20 ml syringe. 3. Turn the vial with the attached syringe upside-down and draw up the solution into the syringe. 4. After removing the filter, inject the solution intravenously at a slow speed: Initially 1 ml per minute, not faster than 2 - 3 ml per minute. 5. The filter needle is for single use only. Always use a filter needle when drawing up the preparation into a syringe. - No blood must flow into the syringe due to the risk of formation of fibrin clots.

References:

1. Guidelines on Oral Anticoagulation. Haemostasis and Thrombosis Task Force. BCSH third edition 2005 update.

2. Guidelines for use of FFP, Cryoprecipitate and Cryosupernatant. BCSH 16.01.04

By:Dr.Rania Abdalla

How is ectopic pregnancy treated?

>> Medical therapy : single dose of methotrexate is best used for those are asymptomatic,whose B.HCG is<5000mIU/ml,have tubal size cm,have no fetal cardiac activity on ultrasonography ,and will come in to be followed closely. ...Despite low and declining B.HCG levels,tubal rupture can still occur with methotexate treatment.With sever pelvic pain,monitoring of vital signs and hematocrit can help differentiate between tubal abortion and tubal rupture. Most common side effects of methotrexate are (1)stomatitis,(2)conjuncivitis,(3)mild abdominal pain of short duration.Rare side effects include dermatitis and pleuritis.

>> Surgury (laprotomy) : is done only if transvaginal ultrasonography shows an heterotopic pregnancy(intrauterine and ectopic pregnancy together) or the pt. unstable,or the criteria for medical or expectant mangement is not fullfild.. >> Laproscopic surgery has been found to be superior to laprotomy and can treat most patients. .. Persistent ectopic pregnancy refers to the continued growth of trophoplastic tissue after surgery.Special attention should be given the proximal portion during surgery and the ectopic pregnancy should be flushed out with suction irrigation. >> Exepectant management is done when ectopic pregnancy is suspected ,but transvaginal ultrasonography does not show an ectopic pregnancy .The patient is followed with weekly ultrasonography and weekly B.HCG measurements until the level is < 10 mIU/mL. >>All pregnant women who are Rh-negative should receive Rh immunoglobulin.

CLUBBING...........

1. Respiratory: C-Chronic Lung Suppuration: ABC: A-Abscess, Empyema ...B-Bronchiectasis C-CF (Cystic Fibrosis) C-CFA (Cryptogenic Firbosing Alveolitis) C-Cancer: Bronchongenic Carcinoma, Mesothelioma

2. GIT causes: C-CD (Crohn's Disease), IBD (CD>UC) C-Cirrhosis C-Coeliac disease C-Cancer: GI Lymphoma

3. Cardiac Causes: C-CCHD (Cyanotic Congenital Heart Disease)

C-Carditis (Infective Endocarditis) C-Cancer: AM (Atrial Myxoma)

{4. Rare Causes: Thyroid acropachy Familial Unilateral Clubbing: (Remember only 2A).... AAA (Axillary Artery Aneurysm) AVM (Brachial AV Malformations)}

profuse, watery diarrhoea: cholera prolonged, non-bloody diarrhoea: Giardia bloody diarrhoea:, vomiting, abdo pain: Shigella ...severe vomiting: Staphylococcus aureus

- The most common cause is Compylobacter then Salmonella - CASES = Campylobacter, Amoeba, Shigella, E coli (invasive and hemorrhagic ), Salmonella >> Bloody diarrhea - Cryptospordia, isospora, Giardia, Vibrio coleri, Viral >> Watery diarrhea - WBCs in the stool means invasive organism " CASES" - CASES = Each need culture to be diagnosed - Cryptospordia needs ( Modified acid fast test ) - Giardia ( ELISA or Stool antigen ) - Cryptospordiia and Giardia may be detected as ova or prasite from the stool - Clostridium difficle needs ( stool toxins )

- Shigella & E coli O157 H7 >> HUS - Bacillus cereus & Staph aureus food poisoning >> Mainly vomiting

- Cryptospordia >> Common in HIV - Compylobacter >> Gullian barre, Reactive arthritis