Bleeding disorders 24/8/2020 - PowerPoint Presentation

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Bleeding disorders

24/8/2020

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Bleeding Disorders

• Abnormal coagulation cascade

Hemophilia, Vitamin K deficiency

• Abnormal platelets

Bernard-

Soulier

Glanzmann’s

Thrombasthenia

ITP, TTP

, HUS ,

• Mixed Disorders

Von

Willebrand

Disease,

DIC

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Type of Bleeding

• Abnormal

platelets

Mucosal

bleeding,

skin bleeding,

petechiae

•

Abnormal

coagulation factors

-

Joint bleeding, deep tissue bleeding

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Labs tests :1- Bleeding

Time

• Test of

platelet

function2- PTT 3- PT 4- Thrombin Time

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Glanzmann’s

Thrombasthenia

:

Autosomal recessive disorderdeficiency of GPIIb/IIIa receptors present

with bleeding symptoms in

childhood.

-Blood smear: Isolated platelets (no clumping) Absent platelet aggregation in response to stimuli platelet aggregometry

Bernard-Soulier Syndrome Autosomal recessive disorderpresent with bleeding symptoms in childhood.deficiency of GPIb plt receptors :- Platelets cannot bind vWF Also results in large platelets Key lab findings: - Prolonged bleeding timeThrombocytopenia - Large platelets on blood smear

- Wiskott-Aldrich Syndrome : -plt and Immunodeficiency syndrome of infants- X linked disorder of WAS gene (WAS protein) * Necessary for T-cell cytoskeleton maintenance

Inherited Platelet Disorders

•

Immune dysfunction

↓ platelets

Eczema

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Giant Platelets

Can

be seen in association with thrombocytopenia

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1- ITP (Idiopathic thrombocytopenic purpura

)

*immune-mediated

destruction of platelets and possibly inhibition of platelet release from the megakaryocyte caused by anti-GPIIB/IIIA antibodies : Consumption in splenic macrophages

Splenomegaly

Thrombocytopenia acquired platelet disorder

In children, it is usually an acute disease, most commonly following an infection, and with a self-limited course. In adults, it is a more chronic disease, although in some adults, spontaneous remission occurs,

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Diagnosis of exclusion

Rule out other causes of bone marrow suppression

characterized by

:

mucocutaneous bleeding and a low, often very low, platelet count, with an otherwise normal peripheral blood cells and smear. - Laboratory testing for antibodies (serologic testing) is usually not helpful due to the low sensitivity and specificity of the current tests Large plts on

perepheral

smear

• Treatment: Initial treatment in patients without significant bleeding symptoms, severe thrombocytopenia (<5000/μL) or signs of impending bleeding (such as retinal hemorrhage or large oral mucosal hemorrhages) can be instituted as an outpatient using single agents. - Steroids

- IVIG (blocks Fc receptors in macrophages) - Splenectomy

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2- TTP

Thrombotic thrombocytopenic

purpura

• Disorder of

small vessel thrombus formation

• Consumes platelets

==< thrombocytopenia • ↓ activity of vWF cleaving protease ADAMTS13

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Cause

• Severe ADAMTS13 deficiency

,

Usually <10% normal activity

• Usual cause: acquired autoantibody to ADAMTS13 - Result: vWF multimers in areas of high shear stress ,- Obstruction small vessels

Microangiopathic

hemolytic anemia • Hemolytic anemia (↑LDH, ↓ haptoglobin) • Caused by

shearing of RBCs as they pass through thrombi in small vessels • Blood smear: schistocytes • Seen in: TTP HUS DIC

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Clinical symptoms :

Fever

•

Neurological symptoms

: Headache, confusion, seizures • Renal failure • Petechiae and bleeding

Non-specific

Lab tests:

• Hemolytic anemia

• Thrombocytopenia • Schistocytes on blood smear • PT/PTT should be normal • Contrast with DIC • May see elevated d-dimer Treatment • Plasma exchange: removes antibodies • Platelet counts monitored to determine efficacy

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3-HUS

Hemolytic

Uremic Syndrome

• Many similarities with TTP

• Also caused by platelet-rich thrombi in small vessels • MAHA, thrombocytopenia, acute kidney injury (Renal thrombi =< kidney injury )• Usually no fever or CNS symptoms •

Commonly seen in

children

, follow GI infection E. Coli( Shiga-like toxin causes microthrombi )

Treatment of HUS is primarily supportive. In HUS associated with diarrhea, many (~40%) children require at least some period of support with dialysis Plasma infusion or plasma exchange has not been shown to alter the overall course. ADAMTS13 levels are generally reported to be normal in HUS In patients with aHUS, eculizumab, a humanized monoclonal antibody against C5 that blocks terminal complement, has efficacy in resolution of HUS and improving or preserving renal function

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DIC Disseminated Intravascular

Coagulation

• Widespread activation of clotting cascade

leading to Diffuse thrombi (platelets/fibrin) =< ischemia • Consumption of clotting factors and platelets • Destruction of red blood cells=

<

anemia • Elevated PT/PTT/Thrombin time

- Consumption of factors • Low platelets - Consumption of platelets • Low fibrinogen (consumption) • Microangiopathic hemolytic anemia • Low RBC (anemia) • Schistocytes on blood smear

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Occurs secondary to another process

:

• Obstetrical emergencies

: (

Amniotic fluid contains tissue factor) : abruptio placenta , major haemorrhagic bleeding , can develop DIC . • Sepsis : 1- Endotoxin –> activates coagulation cascade

, 2-

Cytokines Cancer: (well-described hypercoagulable state) Excess coagulation: DIC

-Leukemia :acute promyelocytic leukemia (APML) • Rattlesnake bites :Thrombin-like glycoproteins within venom • Treatment: underlying disorder • Fresh frozen plasma: replace clotting factors • RBCs, platelets • Cryoprecipitate (for low fibrinogen)

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Von Willebrand

Disease

Most

common inherited bleeding disorder : Affects up to 1 percent of population • Gene mutations =< ↓ level or function of vWF

• Most cases

autosomal dominant (males=females) Clinical symptoms : Usually mild, non-life-threatening bleeding

• Easy bruising • Skin bleeding • Prolonged bleeding from mucosal surfaces -Severe nosebleeds - Menorrhagia Diagnosis • Normal platelet count • Normal PT • Increased PTT (depending on severity) Usually no joint/deep tissue bleeding • Increased bleeding time

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Diagnosis • Ristocetin

cofactor activity

assay

Treatment • vWF concentrate • Desmopressin

: Analogue of vasopressin (ADH) with no

pressor activity , Increases vWF and factor VIII levels , Releases vWF from endothelial cells• Aminocaproic acid

: Antifibrinolytic drug , Inhibits plasminogen activation =< plasmin = Less breakdown of formed clots

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Heyde’s Syndrome?

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Hemophilias • X-linked recessive diseases

• Gene mutations: Run in families; also occur de

novo( 30%)

•

Hemophilia A: Deficiency of factor VIII • Hemophilia B: Deficiency of factor IX ( Also called Christmas disease )

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• Present with spontaneous or easy bruising

• Recurrent

joint bleeds is common presentation

• Screening:

PTT will be prolonged Factors VIII, IX both part of intrinsic pathway • PT, bleeding time, platelet count all normal

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Treatment

1-

Replacement factor VIII and

IX

2-NONTRANSFUSION THERAPY IN HEMOPHILIA * Desmopressin (dDAVP

)

• Used in mild

hemophilia A Antifibrinolytic Drugs : Aminocaproic acid

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Coagulation Factor Inhibitors

• Antibodies

,

Inhibit activity or increase clearance of clotting factor

• Inhibitors of factor VIII most common • Often occur in association with: - Malignancy - Post-partum - Autoimmune disorders

Can be treated with

prednisone Can present similar to hemophilia • Deficient activity of VIII= bleeding

, Prolonged PTT • Mixing study will differentiate from hemophilia A

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Vitamin K Deficiency •

Results in

bleeding

• Deficiency of vitamin K-dependent factors

: II, VII, IX, X • Key lab findings: Elevated PT/INR , Can see elevated PTT (less sensitive) • Normal bleeding time

*Dietary

deficiency

rare :(: GI bacteria produce sufficient quantities) • Common causes: -Warfarin -

Antibiotics (deplete GI bacteria) - Newborns (sterile GI tract) - Malabsorption (Vitamin K is fat soluble)

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Thank you