Bleeding Diathesis

Thamir .D Alotaify1100020

Bleeding disorders • Def / a group of hematological diseases

interfer with normal hemostasis • Types : - Hypocoagulability - hypercoagulability ( bleeding tendency) ( thrombosis tendency )

Normal hemostasis In case of hemorrhage , there will be normal

responce to stop the bleeding 1- vasocostriction : Due to :A- direct myogenic spasm B- platelet ( throboxane A2)C- neuronal

2- platelet pulg

• Mechanism :When there is an endothelial injuryPlatelet aggregation will takes place When the platelets attatched to each other they

will be activated and platelet pulg will occures

3 -coagulation cascade

• 1- coagulation factors • 2- prothrombin • 3- Ca+

1-Vasopathies

• I. Congenital• • Telangiectasiae (Rendu-Osler-Weber disease)

• Aneurysm of fine vessels • Ehlers-Danlos syndrome, Marfan’s syndrome, retinocerebral angiomatosis (von Hippel-Lindau syndrome), encephalotrigeminal angiomatosis (Sturge-Kalisher-Weber syndrome)

• II. Acquired• • Hemorrhagic vasculitis – Henoch-Schönlein purpura

• Immune vasculitis• Systemic vasculitis• Avitaminosis of vitamin C

2 -platelet abnormalities:

• Hypocoagulability :2- platelet abnormalities :Decrease platelet count → increases bleeding time a) Viral infections b) Bone marrow failure c) ITP d)TTP e) Drugs f) Antiphospholipid syndrome

3 -Coagulation factors abnormalities

1- anticoagulant drugs 2- decrease production ( hepatic failure )3- nephrotic syndrome4- sepsis 5- vitK defeciency 6- genetic ( hemophilia )

•I. Congenital• Deficiency of coagulation factor VIII (hemophilia A)• Deficiency of coagulation factor IX (hemophilia B)• Deficiency of coagulation factor XI (hemophilia C)• Deficiency of other coagulation factors (I, II, V, VII, IX, X and XIII) • Deficiency of XII factor, prekallikrein or kininogen, protein C and S (without excessive bleeding)• von Willebrand’s disease (angiohemophilia)

CLINICAL FEATURES OF BLEEDING DISORDERS

BYDR.ABDULRAZAQ HUDHAIRI AL-HAZEEMI

CONSULTANT NEUROSURGEONGERMAN BOARD

SOONID:1100022

Purpura is the appearance of red or purple discolorations on the skin that do not blanch on applying pressure(3–10 mm).A petechia is a small (1 - 2 mm) red or purple spot on the body.An ecchymosis is subcutaneous purpura larger than 1 centimeter .Hemarthrosis is a bleeding into joint spaces.A hematoma is a localized collection of blood outside the blood vessels.

Terminology

Clinical Features of Bleeding Disorders

Platelet Coagulation disorders factor disorders

Site of bleeding tissues Skin Deep in soft Mucous membranes (joints, muscles) (epistaxis, gum, vaginal, GI tract)

Petechiae Yes No

Ecchymoses (“bruises”) Small, superficial Large, deep

Hemarthrosis / muscle bleeding Extremely rare Common

Bleeding after cuts & scratches Yes No

Bleeding after surgery or trauma Immediate, Delayed (1-2 days), usually mild often severe

Platelet Coagulation

Petechiae, Purpura Hematoma, Joint bl.

Petechiae(typical of platelet disorders)

Hemarthrosis

Hematoma

Petechiae

Purpura

Ecchymosis

Senile Purpura

Solar purpura or Senile purpura is a skin condition characterized by large, sharply outlined, 1- to 5-cm, dark purplish-red ecchymoses appearing on the dorsa of the forearms and less often the hands.The condition is most common in elderly white persons. It is caused by sun-induced damage to the connective tissue of the skin.

Petechiae in patient with Rocky Mountain

Spotted Fever

Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by the organism Rickettsia rickettsii.

Henoch-Schonlein purpura

Henoch-Schoenlein purpura is an acute immunoglobulin A (IgA)–mediated leukocytoclastic vasculitis that primarily affects children.

Ecchymoses

(typical of coagulation factor disorders)

Coagulation profile

Amir Mohammed

Coagulation ProfileOVERVIEW

•Prothrombin Time•Activated Partial Thromboplastin Time•Thrombin Time•Fibrinogen•Fibrin Degradation Products (FDP’s)•APTT 50% NP•Retiplase Time•Euglobin Lysis Time•Urea solubility Test

PROTHROMBIN TIME• This measures the clotting time of plasma after the

addition of brain extract containing tissue thromboplastin.• This will test the extrinsic clotting pathway involving

factors V, VII, X and Fibrinogen.• The reference range for prothrombin time depends on the

analytical method used, but is usually around 12-13 seconds

• Prolongation of the Prothrombin Time is seen in,1) Liver cell dysfunction2) Vitamin K deficiency3) Warfarin therapy4) Disseminated Intravascular Coagulation (DIC)

ACTIVATED PARTIAL THROMBOPLASTIN TIME

• This will test for defects in the extrinsic pathway.• The clotting factors are Factors, XII, XI, IX, VIII, X, V, II

and I• The typical reference range is between

30 seconds and 50 s• Prolongation of APTT is seen in, Haemophilia A and B (Factors VIII and IX) Von Willebrandt's Disease (stabilizing factor for factor VII ed) Other factor deficiencies (XII, XI) Liver failure Disseminated Intravscular Coagulation.

THROMBIN TIME• thrombin added to undiluted plasma• tests the conversion of fibrinogen -> fibrin• The reference ranges of the Thrombin Clotting

time is generally <22 seconds,• prolonged in: -> heparin

-> DIC-> hypofibrinogenaemia-> fibrin degradation products

FIBRINOGEN• normal: 1.5-4.0• high in: acute phase response• low in: -> sepsis

-> DICFIBRIN DEGRADATION PRODUCTS (FDPs)• marker of fibrin and fibrinogen breakdown• The reference range of FDP levels is less than 10

mcg/mL (conventional units) or less than 10 mg/L (SI units).

APTT 50% NP• mixing of patients sample with pooled normal plasma – 50:50

mix• failure to correct after mixing:• -> lupus anticoagulant

ECHIS TIME• snake venom from Echis multisquamatus added to sample• differentiates liver dysfunction from vitamin deficiency• this activates prothrombin without requiring vitamin K• is normal in vitamin K deficiency or warfarin use• The reference ranges is 10.5 - 15 sec• if prolonged: -> factor deficiency (liver disease)

RETIPLASE TIME• used to detect deficiency or abnormalities in

fibrinogen• snake venom that has similar action to thrombin but

is resistant to inhibition by antithrombin III• interpret with TCT• if retiplase time normal and TCT prolonged: -> heparin

-> hirudin-> direct thrombin inhibitors

EUGLOBIN LYSIS TIME• shortened time:• -> presence of systemic fibrinolytic pathway

activatorsUREA SOLUBILITY TEST• factor 13 stabilises fibrin• if deficient 5M urea will dissolve it

Treatment

By:fahad saad alenzi1100026

• Children:• Children do not usually require treatment, Where

this is necessary on clinical grounds.• high-dose prednisolone is effective, given for a very

short course.• Intravenous immunoglobulin (i.v. IgG) should be

reserved for very serious bleeding or urgent surgery.• Chronic ITP is rare and requires specialist

management.

• Adults:• Patients with platelet counts greater than

30 × 10^9/L require no urgent treatment unless they are about to undergo a surgical procedure.

• First-line therapy :• consists of oral corticosteroids 1 mg/kg body weight.• Approximately 66% will respond to prednisolone but relapse

is common when the dose is reduced. • Only 33% of patients can expect a long-term response and

long term remission is seen in only 10–20% of patients following stopping prednisolone.

• Patients who fail to respond to corticosteroids or require high doses to maintain a safe platelet count should be considered for splenectomy.

• Intravenous immunoglobulin (i.v. IgG) is effective, It raises platelet count in 75% and in 50% the platelet count will normalize , Responses are only transient (3–4 weeks) with little evidence of any lasting effect.

• However, it is very useful where a rapid rise in platelet count is desired, especially before surgery.

• There are also advocates for high dose corticosteroids for additional therapy.

• Second-line therapy: involves splenectomy, to which the majority of patients respond – two-thirds will achieve a normal platelet count.

• Patients who do not have a complete response can still expect some improvement.

• Third-line therapy; For those that fail splenectomy, • a wide range of other therapies are available,• These include; highdose corticosteroids, intravenous immunoglobulin, vinca alkaloids, danazol, Immunosuppressive agents such as ciclosporin and dapsone. combination chemotherapy, mycophenolate mofetil.

• Major difficulties with many third-line therapies are modest response rates and slow onset of action, Consequently ,there is also interest in the use of specific monoclonal antibodies such as rituximab, as well as recombinant thrombopoietin.

• However, clinical trials of thrombopoietin were stopped because of thrombocytopenia but eltrombopag a thrombopoietin receptor agonist (which binds to another point of the thrombopoietin receptor), has been shown to increase platelets in ITP.

• Romiplostim ; a novel thrombopoiesis protein given weekly subcutaneously, has also been shown to significantly increase platelet count in ITP on a long-term basis, there were no major adverse effects in this trial.

• Platelet transfusions are reserved for intracranial or other extreme haemorrhage, where emergency splenectomy may be justified.