Bleeding Disorders

Dr.Hisham Abid AldabbaghMSc. Internal Medicine

Kingdom of Saudi ArabiaMinistry of HealthDirectorate of Health Affairs in Gurayat Gurayat General Hospital

Causes of Mild Bleeding Disorders

• Inherited causes:

1- partial deficiencies of coagulation factors;VIII,IX, and XI2- fibrinolytic proteins disorders3- defects or deficiencies in von Willebrand factor4- platelets problems5- connective tissue problems (e.g., Ehler-Danlos syndrome).

Sorry, you have r• Acquired causes:

1- autoimmune thrombocytopenia 2- acquired bone marrow disorders3- hemorrhagic side effects of antiplatelet or anticoagulant drugs 4- acquired deficiencies (commonly of factor VIII or von Willebrand factor)5- thyroid disease, Cushing’s syndrome, liver and renal disease.

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Clinical Manifestations of Mild Bleeding Disorders

• vary and depend on the nature of the defect and its relative severity.

• mild bleeding disorders are most troublesome at times of significant hemostatic challenges.

• The timing of abnormal bleeding help to distinguish the delayed-onset bleeding problems more typical of deficient/defective coagulation or fibrinolytic proteins from immediate bleeding and bruising problems typical of defects in von Willebrand factor or platelets.

• Some symptoms (e.g., nosebleeds, menorrhagia) are not specific to any one type of bleeding problem.

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Items of value in bleeding histories :

1- the family history of bleeding 2- the type of bleeding problem 3- whether the problems are lifelong or recently acquired without a history of bleeding when challenged earlier in life4- Questions about excessive bleeding, and its timing, with surgery, dental extractions and trauma.

Prevalence of mild bleeding symptoms

Symptom Prevalence)%( Bruising

Abundant bruising or bleeding 26Bruising without reason 34

Bruising disproportionate to trauma 12

Bruises that spread towards feet and/or ≥ an orange in size <1

Nosebleeds 24 Yes and with the following features:

Longer than 15 minutes 56Requiring cautery 24

Bleeding with dental extractions 74 Yes and with the following features:

Abnormal bleeding 35

Bleeding     > 24 hours afterwards 8

Bleeding problems with surgeries 9Excessive bleeding after accidents 39

Women

Abundant menstrual bleeding 56

Menses longer than 7 days 7

• Mild bleeding disorders may not be apparent until the individual is exposed to significant challenges (e.g., major surgery), and the problem may not be manifest with all challenges.

• Gender has an influence on the manifestations of mild bleeding disorders. Females are more commonly referred for evaluation because of troublesome bleeding with menses and/or childbirth

A staged approach to diagnostic testing for mild bleeding problems.

First assessment:Complete blood count with blood film evaluation

ABO blood group

Ferritin

PT, PTT, INR

if abnormal, investigate for factor deficiencies if hemophilia or other factor deficiencies strongly suspected, do factor VIII, IX, XI assays

Thrombin clotting time and clottable fibrinogenif abnormal, evaluate reptilase time and measure fibrinogen antigen

Von Willebrand disease screenfactor VIII, von Willebrand factor antigen and ristocetin cofactor levels multimers if screen is abnormal

Platelet aggregation and secretion tests

Evaluate for platelet dense granule deficiency (first or subsequent assessment)

Consider tests for renal problems, liver or thyroid disease, if appropriate

Subsequent assessment:

Confirm and further evaluate abnormalities identified on the first assessment

Evaluate platelet secretion (or dense granules) if a platelet-type bleeding disorder is suspected but notdiagnosed by initial tests, or if the aggregation abnormalities suggested a secretion or dense granuleproblem.

Consider tests for rarer disorders (e.g., Scott’s syndrome) if no abnormalities are found

If the history suggests delayed bleeding problems, and no diagnosis was established, exclude milddeficiencies (factors VIII, IX, XI first) by factor assays and consider other tests (e.g., partial alpha2plasmin inhibitor deficiency)

Commonly Faced Problems in Management of Mild Bleeding Disorders• There are trade-offs to consider between benefits and adverse effects

of therapy, such as an increased risk of thrombosis (for example, with fibrinolytic inhibitor therapy or from withholding perioperative anticoagulant prophylaxis) and of hyponatremia and seizures with desmopressin.

• Therapies may, however, offset adverse events, related to hemorrhage, and reduce the need for blood product support (with transfusion reaction/infectious risks).

• Potential risks/benefits of therapy need to be considered carefully, particularly when the efficacy of treatments or prophylaxis for mild bleeding problem are unknown and unverifiable, or if there are thrombotic risks.

• Mild factor VIII deficiency, platelet function defects, von Willebrand factor deficiency, and some other mild bleeding problems (e.g., Ehler-Danlos syndrome) can be managed successfully with fairly simple maneuvers, such as desmopressin (DDAVP) prior to surgery.

• For many mild bleeding disorders, fibrinolytic inhibitor therapy with Amicar or Tranexamic Acid is used for dental and oral surgeries and it may reduce bleeding with other operative procedures. Fibrinolytic inhibitor therapy is also helpful for treating some rarer disorders.

• Mild factor IX deficiency and rare recessive coagulation disorders may need replacement therapies with major procedures.

• With drug therapy for mild platelet function problems, platelet transfusions are rarely needed.

• For women with mild bleeding disorders, treatment may be needed to

control menorrhagia or prevent abnormal bleeding with childbirth and epidural anesthesia.

• The choices for menorrhagia management need to be tailored to patient preferences and include oral contraceptives, fibrinolytic inhibitors, intrauterine devices designed to reduce menorrhagia, DDAVP, endometrial ablation and hysterectomy.

• Drugs that inhibit platelet function (e.g., aspirin, clopidogrel) and anticoagulants can unmask or induce mild bleeding problems. Desmopressin improves in vitro hemostatic abnormalities induced by anti-platelet therapies.

• Bleeding from Cushing syndrome and thyroid disease require correction of the endocrine abnormality, whereas bleeding from uremia is often managed by correction of anemia.

Treatment Options

- Factor cncentrates• Factor concentrates are the ideal and safest treatment for rare bleeding

disorders. • Factor concentrates are administered intravenously.• VIII concentrate: 10-50 unit/kg

- Prothrombin complex concentrate (PCC)• Indicated for urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonists (VKA, eg, warfarin) therapy

• Administer vitamin K concurrently to maintain vitamin K-dependent clotting factor levels once the effects of prothrombin complex concentrate have diminished.

• Dosing is based on pretreatment INR obtained close to time of dosing- INR 2 to 4: 25 units/kg- INR 4-6: 35 units/kg- NR >6: 50 units/kg• Unlike plasma, does not require blood group typing or thawing, so it can be

administered more quickly than frozen plasma• Administered intravenously, in a significantly lower volume than plasma at

recommended doses.

- Fresh Frozen Plasma

- FFP: 10-20 mL/kg of body weight will increase factor levels by 20-30%• Frequency of transfusion depends on the half-life of the deficient

factor(s)• Infusion rate:2 to 3 mL/kg/hour (ie, approximately one unit in 1.5 hours)• Number of units = Desired dose (mL) / 200 mL/unit- Octaplas: 10-15 mL/kg IV initially; this should increase plasma coagulation factors by ~15-25%• If hemostasis not achieved, use higher doses and adjust dose based on

desired clinical response• Administer based on ABO-blood group compatibility

Indications of Plasma transfusion

• Replacement of multiple coagulation factors in patients with acquired deficiencies due to liver disease or those undergoing urgent invasive procedures

• Massively transfused patients who have clinically significant coagulation deficiencies and hypovolemia

• Patients on warfarin therapy with bleeding or that need to undergo an invasive procedure before vitamin K could reverse the effects of warfarin or who need only transient reversal of warfarin effects

• For transfusion or plasma exchange in patients with thrombotic thrombocytopenic purpura (TTP) and some cases of hemolytic uremic syndrome

• Management of patients with selected coagulation factor deficiencies, congenital or acquired, for which no specific coagulation concentrates are available (i.e., factors II, V, VII, X, XI, Proteins C or S*

• Management of patients with rare specific plasma protein deficiencies, such as C1 inhibitor, when recombinant products are unavailable*

- Cryoprecipitate• Cryoprecipitate contains factor VIII, fibrinogen (factor I), and a few other proteins

important for blood clotting.

• It contains higher concentrations than FFP of some (but not all) coagulation factors, so less volume is needed. Cryoprecipitate is administered intravenously. 1unit per 5-10kg of patient weight every 8-12 hours. It is indicated for:

• Fibrinogen Replacement• Factor XIII Replacement• Factor VIII Replacement• von Willebrand Factor Replacement

-Desmopressin

• Intravenous• Hemophilia A & Von Willebrand Disease• Hemophilia with factor VIII levels greater than 5%; von Willebrand disease

(type I)

• 0.3 mcg/kg IV over 15-30 minutes IV (for pre-op, 30 min before procedure) • Intranasal (Stimate)• <50 kg: 150 mcg; for pre-op, give 2 hr before procedure• >50 kg: 300 mcg; for pre-op, give 2 hr before procedure

-Thrombin

• Powder for topical solution, spray kit, pad, and topical solution• Indicated for hemostasis whenever oozing blood and minor bleeding from

microvessels is accessible• Dose depends on area to be treated• Apply on surface of bleeding tissue (solution or spray)• Severe bleeding: Concentrations of 1000-2000 units/mL (Thrombin-JMI) • Mild/moderate bleeding: Concentrations of 100 units/mL (Thrombin-JMI) for

general use (plastic surgery, dental, skin grafts etc)• Apply pad (Thrombi-Pad) dry or wetted with up to 10 mL of 0.9% sodium

chloride directly over source of bleeding.• Apply powder (Thrombin-JMI) directly to the bleeding area or on oozing surfaces• May soak in up to 10 mL of absorbable gelatin sponge (Evithrom) applied on

bleeding surface

-Antifibrinolytic drugsTranexamic Acid and Aminocaproic Acid

• indications:• to hold a clot in place in certain parts of the body, such as the

mouth, bladder, and uterus.• during dental work, but are not effective for major internal

bleeding or surgery. • factor XI deficiency. • control excessive menstrual bleeding. 1300 mg PO TID for up to 5

days during menstruation• Antifibrinolytic drugs can be administered orally or by injection• Need adjustment in renal impairment

- Platelet transfusion

• Typical dosing is 6 units of platelets. This is expected to raise the platelet count by 30,000-60,000/uL in a 70 kg patient.

• Transfused platelets have a short life span and will need to be re-dosed within 3-4 days if given for prophylaxis.

• Platelet transfusions may be given for thrombocytopenia or platelet dysfunction to treat active platelet-related bleeding or as prophylaxis in those at serious risk of bleeding.

• Platelet transfusions are sometimes used to treat factor V deficiency.• Administer based on ABO-blood group compatibility**

- Fibrin glueFibrin glue can be used to treat external wounds and during dental work, such as a tooth extraction. It is not used for major bleeding or surgery. It is applied to the bleeding site.- Vitamin K

Treatment with vitamin K can help control symptoms of inherited combined deficiency of the vitamin K-dependent clotting factors (VKCFD).

- Hormonal ContraceptivesHormonal contraceptives (birth control pills) help control menstrual bleeding.- Intra-uterine devices (IUDs)Intra-uterine devices (IUDs) help control menstrual bleeding.

Professional message

Dear Colleagues; please,

• Be quiet, when you are faced with bleeding disorder• Always, look for the actual reason of bleeding disorder• Don’t miss, the hidden causes• Follow, stepwise way in approaching bleeding disorders• Don’t worry, you have a lot of management options for bleeding

disorders• Be intelligent, in choosing the most effective option for each individual

case of bleeding disorders; for time-saving and so life-saving

Great Thanks for joining in management of bleeding disorders

For more information, please connect with:- American Society of Hematology- Medscape reference- WebMD- MedlinePlus- Drug.com- Hemophilia Federation of America