Lecture 12: Abnormal Bleeding

Immunoglobulin A-associated vasculitis (Henoch-Schonlein pupura)

IgA immune complex deposition

Mostly in kids, following a viral URI

Triad: palpable purpura on extremities/buttock, joint pain, abdominal pain (intussusception)

Thrombocytopenia occurs by four mechanisms

Decreased bone marrow production

Increased destruction

Dilution

Combination

Idiopathic (autoimmune) Thrombocytopenic Purpura (ITP)

Acquired → production of IgG antiplatelet antibodies are stimulated (GpIIb/IIIa) → inhibits platelet aggregation

Acutely – children, usually < 10 years of age (more COMMON)

Usually preceded by a viral syndrome

Self-limited - 90% spontaneous remission, usually within 2 months

Chronic – adult form

Much more common in women

Usually no identifiable cause

Course unpredictable, almost always lasts longer than 6 months

ITP Clinical Findings

Petechiae/purpura

Bruising

Increased bleeding: nose bleeds, heavy menstruation, gums bleeding, blood blisters

ITP Labs

CBC, PT, PTT, peripheral smear (all patients)

Hepatitis C/HIV in adults

ITP Diagnosis and Treatment

Decreased platelet count

Increased bleeding time

Normal PT/PTT

Normal kidney function

Glucocorticoids (dexamethasone or prednisone)

Thrombotic Thrombocytopenic Purpura (TTP)

Thrombocytopenia, microangiopathic hemolytic anemia, acute renal failure

Neurologic symptoms, fever

red cell lysis/schistocytes

Thrombocytopenic purpura

Fluctuating neurologic symptoms

Inhibition of ADAMTS13 (cleaves von willebrand factor) → Increased platelet aggregation/adhesion causes thrombi

Majority diagnosed are 40–50-year-old females

Thrombotic Thrombocytopenic Purpura (TTP) causes

Congenital deficiencies

Numerous drugs such as quinine (beverages such as tonic water and bitter lemon)

Antiplatelet agents

Chemotherapeutics

Malignancy

Cardiovascular surgery

Pregnancy

Thrombotic Thrombocytopenic Purpura (TTP) Diagnosis and Treatment

Decreased platelet count

Increased bleeding time

Decreased kidney function

Anemia

Peripheral smear: Schistocytes

Normal PT/PTT

Medical emergency

Plasma exchange (FFP), glucocorticoids and possibly immunosuppressive agents

Hemolytic Uremic Syndrome

Renal dysfunction – possibly failure (worse Cr → uremia – more likely HUS)

Children with history of bloody diarrhea

Causes: Shiga toxin-producing bacteria

Hemophilia A (Classic Hemophilia)

Factor VIII deficiency

X-linked recessive

lifelong history of bleeding:

Deep muscles and joints are most common sites

Skin bruising, GI, GU, intracranial bleeding

Spontaneous bleeding

Patients seldom bleed from small cuts or venipuncture sites, but hemorrhage out of proportion to injury occurs after larger injuries

Bleeding maybe delayed up to 48 hours after injury

Hemophilia A Diagnosis and Treatment

Normal platelet count

Normal or increased bleeding time

Normal PT

Abnormal PTT (intrinsic pathway)

Decreased Factor VIII

Treatment: Desmopressin, give factors (monoclonal antibody-purified or recombinant factor product)

von Willebrand’s Disease

autosomal dominant

decrease or impairment in action of von Willebrand factor

primary hemostasis by binding to platelets

VWF → fibrin clot formation by as carrier protein for factor VIII

Easy bruising, Skin bleeding

Prolonged bleeding from mucosal surfaces

Normal platelet count

Increased bleeding time

Normal or Increased PTT (depends on how much VIII is affected)

Normal PT

Von Willebrand Factor Antigen: decreased

von Willebrand’s Disease Treatment

For minor bleeding or minor surgery – intravenous or intranasal desmopressin (DDAVP)

If bleeding is not adequately controlled, a von Willebrand factor (VWF) concentrate should be used

Disseminated Intravascular Coagulation

bleeding is from loss of: Platelets, Clotting factors, Fibrinolysis, Mechanical RBC destruction, Small vessel occlusion from fibrin deposition

SUSPECTED IN ANY PATIENT WITH: Purpura; bleeding tendency; and signs of multiple organ injury

Disseminated Intravascular Coagulation Causes

Snake bites, Sepsis from gram - bugs

Trauma, obstetric issues, pancreatitis, malignancy, nephrotic syndrome, transfusion

Disseminated Intravascular Coagulation Diagnosis

Increased PT

Increased PTT

Decreased platelets

Increased bleeding time

Elevated D-dimer

Decreased factor V and VIII

Elevated fibrin split (degradation) products (d-dimer)

Schistocytes are seen on peripheral smear

Joint Laxity

Ehlers-Danlos Syndromes

Aortic Stenosis

Von Willebrand syndrome

Initial Workup

Complete blood count (CBC) with morphology

Peripheral smear

Coagulation panel:

Prothrombin time (PT) → Extrinsic pathway

Activated partial thromblastin time (aPTT) → Intrinsic pathway