Pathology 1 - Block 3 - Part 5

davidwurbel7's version from 2016-03-29 20:01

Bleeding Disorders

Question Answer
Membrane protein on the platelet that binds to vWF that bridges to the subendotheliumGpIb
Membrane protein on the platelet that bind to fibrinogenGpIIb/IIIa
A simple test of the intrinsic and common pathways of coagulationPartial Thromboplastin Time (PTT)
Test that measures Factors V, VII, X and fibrinogen), three (Prothrombin, Factors VII and X) are vitamin K dependentProthrombin Time (PT)
Hemorrhages 1 to 2 mmPetechiae
Hemorrhages more than 3 mmPurpura
Disease seen in childhood and adolescence. Frequently following upper respiratory tract infection. Pathogenesis - characterized by widespread inflammatory reaction of the capillaries and small vessels purpuric rash, abdominal colic, polyarthralgia, acute glomerulonephritits. Deposition of immune complexes (IgA)Henoch-Schönlein Purpura
Lab Investigations - Platelet count: normal. Bleeding time: normal. Coagulation work-up: normal Urine: proteinuria, microscopic hematuria. Skin biopsy: IgA, C3, fibrin deposits. Renal biopsy: IgA, C3 depositsHenoch-Schönlein Purpura
Clinical features include Vasculitis. Palpable purpura (buttocks & lower limbs). GI bleed. Glomerulonephritis. Self-limited. Responds to steroidsHenoch-Schönlein Purpura
Incidence - seen in children, usually following viral infection Varicella zoster and EBV most common. Pathogenesis - formation of anti platelet antibodies (GpIIb/IIIa). Self limited, resolves spontaneously within 6 months. steroid therapy indicated, if, thrombocytopenia is severeAcute Immune Thrombocytopenic Purpura
Lab findings - thrombocytopenia; bleeding time: prolonged; coagulation study: normalAcute Immune Thrombocytopenic Purpura
Clinical Features - petechial hemorrhages on skin, epistaxis. 80% of children with untreated for the disease have a spontaneous recovery with completely normal platelet counts in 2-8 weeksAcute Immune Thrombocytopenic Purpura
Incidence - young to middle aged women vary from mild to severe. Pathogenesis - formation of ‘auto antibodies’ these are directed against ‘platelet membrane glycoproteins’. Anti-platelet antibodies act as opsonins, that are recognized by IgG Fc receptors on phagocytes. Results in platelet destruction, mostly in spleenChronic Immune Thrombocytopenic Purpura
Lab investigations: Platelet count: decreased. Bleeding time: prolonged. Partial Thromboplastin Time (PTT): normal. Bone marrow: slight increase in megakaryocytesChronic Immune Thrombocytopenic Purpura
Clinical features include easy bruising, menorrhagia, melena, bleed from mucus membranes subconjunctival and retinal hemorrhages maybe seen complications: sub arachnoid hemorrhages, intracerebral hemorrhagesChronic Immune Thrombocytopenic Purpura
Deficiency of enzyme ADAMTS 13 (vWF metalloprotease)Thrombotic Thrombocytopenic Purpura (TTP).
Pathogenesis - absence of vWF metalloprotease would cause an excess of vWF. This increases platelet adhesion in areas of endothelial injury. Therefore thrombus formation occurs with minimal endotheilal injury resulting in thrombocytopeniaThrombotic Thrombocytopenic Purpura (TTP)
Lab Findings: Hb: reduced. White cell count: leukocytosis. Platelet count: reduced. Bleeding time: prolonged. Coagulation studies: normal (PTT is normal). Peripheral blood smear: schistocytes, low platelets Urine: hematuria, proteinuriaThrombotic Thrombocytopenic Purpura (TTP)
Clinical features include fever, thrombocytopenia, renal failure, microangiopathic hemolytic anemia and neurological symptomsThrombotic Thrombocytopenic Purpura (TTP)
Incidence - children (less than 10 years in most cases). Epidemic , summer months, under cooked red meat, unpasteurized milk, contaminated water. May be transmitted from person-person. Common cause for acute renal failure in childrenHemolytic-Uremic Syndrome (HUS)
Pathogenesis - caused by E.coli strain 0157:H7. Shiga like toxin is elaborated which binds and damages endothelial cells in glomerulus. Cytotoxicity of Shiga toxins leads to endothelial cell swelling, abnormal vascular permeability, cell death. Endothelial cell disruption exposes the underlying thrombogenic GBM triggering platelet activation and aggregation, and cytokine activationHemolytic-Uremic Syndrome (HUS)
Lab Findings - Hb: reduced, Platelet count: reduced (thrombocytopenia). Hemoglobulinemia; Haptoglobulin: reduced, there is some amount of intravascular hemolysis; Fibrin degradation product, and D-dimers: present; Peripheral blood smear: schistocytes; Bleeding time: prolonged; Coagulation studies: PTT and PT are normal; Serum creatinine: raised; Urine analysis: proteinuria; Stool examination: EHEC 0157:H7 detected by plating fresh feces on sorbitol-MacConkey agarHemolytic-Uremic Syndrome (HUS)
Clinical Features include acute renal failure, thrombocytopenia, microangiopathic and hemolytic anemia. Infants and young children bloody diarrhea, vomiting, fever, hypertensionHemolytic-Uremic Syndrome (HUS)
A rare autosomal recessive, consanguinity disease. Platelets have a quantitative, or qualitative abnormality of membrane GpIb complex therefore failure to bind von Willebrand factor and thrombin characterized by thrombocytopenia, and giant plateletsBernard-Soulier Syndrome
Clinical Features include bleeding tendency seen early in life or early childhood. Purpura, epistaxis, gingival hemorrhages, menorrhagia. Severe bleed may be sometimes seen. Patients must avoid anti-platelet treatment (aspirin)Bernard-Soulier Syndrome
Lab values CBC: Total platelet count: decreased (usually mild). Peripheral blood smear: giant platelets. Bleeding time: prolonged. Coagulation studies: normal. Platelet aggregation: abnormal study, due to defective adhesion to collagen in vitro. Ristocetin test: abnormalBernard-Soulier Syndrome
A rare, familial, autosomal recessive, consanguinity disease. Bleeding tendency due to quantitative or qualitative abnormalities of platelet receptor GpIIb-IIIaGlanzmann Thrombasthenia
A genetic defect in GpIIb-IIIa can inhibit synthesis of that subunit and prevent normal assembly and processing of the functional receptor. This results in the lack of a fibrinogen receptor and a defective fibrinogen binding after platelet activation. Therefore results in a problem with platelet aggregationGlanzmann Thrombasthenia
Clinical Features include bleeding tendency more in homozygous mutations. Purpura, epistaxis, gingival hemorrhages, menorrhagiaGlanzmann Thrombasthenia
Lab diagnosis - total platelet count: normal. Peripheral blood smear: normal looking platelets. Bleeding time: prolonged. Platelet aggregation: abnormal study. Coagulation studies: normalGlanzmann Thrombasthenia
Disease characterized by a defect of platelet function leading to prolonged bleeding and coagulation defect due to deficiency of factor VIII activity in plasmavon Willebrand Disease
Lab investigations - platelet count: normal; bleeding time: prolonged, (this is due to a platelet adhesion defect); PT: normal; PTT: increased; vWF activity: reduced; Factor VIII activity: reduced; Ristocetin test (Ristocetin cofactor assay): abnormalvon Willebrand Disease
Clinical features include spontaneous bleed from mucous membrane: epistaxis, bleed from trivial wounds, menorrhagia, dental procedures and minor surgeriesvon Willebrand Disease
Assay done by mixing patient’s plasma with formalin fixed platelets and Ristocetin. Ristocetin binds vWF and therefore leads to platelet aggregation. Therefore, the degree to which patient plasma promotes ristocetin-dependent platelet aggregation reflects the vWF activity of the sampleRistocetin Test
Mutation in Factor VIII. X-linked recessive trait. Affects males (and homozygous females). No family history in 30%. Severity depends on amount of Factor VIII activity seen. Typically presents with spontaneous hemorrhagesHemophilia A
Lab investigations - Platelet count: normal; Bleeding time: normal; Prothrombin time: normal; Partial Thromboplastin Time: prolonged; Factor VIII levels: reducedHemophilia A
Clinical features include activity below 1% is associated with severe disease. Easy bruising, hemorrhage following trauma or operative procedures, ‘spontaneous’ hemorrhages to knee joints (hemarthroses), chronic hemophilic arthritis (soft tissue hematomas & hemarthroses) hematuria and bleed into CNS (most serious)Hemophilia A
Decrease in Factor IX activity. Also called as Christmas disease. X linked recessiveHemophilia B
Lab investigations - Platelet count: normal; Bleeding time: normal; Prothrombin time: normal; Partial Thromboplastin Time: prolonged; Factor IX levels: reducedHemophilia B
Complex systemic thrombohemorrhagic disorder. Disseminated intravascular clotting causes a hemostatic defect. Resulting from utilization of the coagulation factors and platelets (consumption coagulopathy)Disseminated Intravascular Coagulation (DIC)
This condition can be seen in obstetric complications (abruptio placentae, amniotic fluid embolism, abortion, intra uterine death) infections (sepsis), neoplasms (mucin secreting adenoca), massive tissue injury and snake bite (viper)Disseminated Intravascular Coagulation (DIC)
Lab diagnosis - Platelet count: decreased. Prothrombin time (PT): prolonged. Partial thromboplastin time (PTT): prolonged. Fibrinogen levels: reduced. Peripheral blood smear: schistiocytes, reduced platelets, polychromatophils. Fibrinogen degradation products: increased; D-Dimers: increasedDisseminated Intravascular Coagulation (DIC)
Treatment - treat underlying cause, volume replacement, correction of hypotension and oxygenation, blood component therapy, heparin (some cases). Need caution as baseline PTT are usually prolonged in patients in DICDisseminated Intravascular Coagulation (DIC)
This is synthesized by the colonic bacteria. Required for synthesis of some coagulation factors Gamma-carboxylation allows procoagulants to actively bind to calcium in fibrin clot formationVitamin K Deficiency


Question Answer
Neither spinal cord nor meninges herniateSpina Bifida Occulta
Spinal cord and/or meninges herniatesSpina Bifida Cystica
Meninges herniatesMeningocele
Meninges + spinal cord herniatesMyelomeningocele
Skin at the site of the defect may be normal, show a dimple, fatty deposits or hair growth, have a birthmark (hemangioma) may be indications ofSpina Bifida Occulta
Symptoms include loss of bladder or bowel control, Partial or complete lack of sensation, Partial or complete paralysis of the legs, Weakness of the hips, legs, or feet of a newborn, Hydrocephalus in 15-25% of children leading to seizures. Deformed feet or legs, such as clubfoot and curved spineMyelomeningocele
Protrusion of meninges and cord forced out by a syrinx (cyst)Syringomyelocele
Most severe type of spina bifida where the spinal cord is open. Neural tissue is only covered by a thin membraneMyelocele (Myeloschisis)
There is a cleft through the entire spine. Complete defect involving the entire spine from top to bottomRachischisis
High levels of Alpha Fetaprotein (AFP) in amniotic fluid and is indicative of possibleNeural Tube Defects
Serious cranial birth defect where a baby is born without parts of the brain and skullAnencephaly
An abnormal increase in CSF within the ventricular system, with the following increase in ICP, Expansion of cerebral ventricles and/or atrophy of the brainHydrocephalus
The most common cause of HydrocephalusAqueductal Stenosis
Genetic disease that causes benign tumors in the brain, but also kidneys, heart, eyes, lungs, and skinTuberous Sclerosis
Cortical tubers, Subependymal nodules (SEN), Subependymal giant astrocytomas (SEGA) which can block ventricular system leading to increase in ICP, Headaches, Blurred vision, NauseaTuberous Sclerosis
Extension of the cerebellar tonsils (the lower part of the cerebellum) into the foramen magnum without involving the brain stemArnold-Chiari Type I
Extension of cerebellar and brain stem tissue into the foramen magnum, and cerebellar vermis only partially complete or absentArnold-Chiari Type II
The cerebellum and brain stem herniate through the foramen magnum and into the spinal cordArnold-Chiari Type III
Involves an incomplete or underdeveloped cerebellumArnold-Chiari Type IV
Enlargement of the 4th ventricle, partial or complete absence of the vermis, and cyst formation in posterior fossaDandy-Walker Syndrome
Degeneration of LMN’s (mostly spinal, only occasionally bulbar), resulting in ‘flaccid’ paralysis, atrophyPoliomyelitis
LMN symptoms only damagePoliomyelitis
Developmental abnormality in formation of the central canal. Usually occurs in cervical segments. Symptoms include - Segmental losses of pain and temperature senses. Some impairment of touch. Expansion of lesion can eventually result in paralysis and atrophy of upper limb musclesSyringomyelia
(Insert 35)

Recent badges