Pediatric Pathology

Disease
Hemolytic Disease of the Newborn

Cause/Risk Factors
Antigen incompatibility between fetus and mother Rh (treatable) ABO (not treatable) Preterm Maternal Diabetes & C Section

Symptoms
Anemia, Liver Failure, Hypoproteinemia CHF (Hydrops Fetalis) Jaundice Immature Lung, Decreased Surfactant Hyaline Membranes Difficult Respiration, Expiratory Grunt Cyanosis, Fine Rales, Ground Glass CXR Retinal Vessel Proliferation on return to room O2 O2 Dependence at 28 days, Persistant Respiratory Distress at 3 months Epithelial Hyperplasia, Squamous Metaplasia Alveolar thickening, Interstitial Fibrosis Abdominal Distension, Tenderness, Ileus, Bloody Diarrhea, Pneumatosis intestinalis Mucosal Sloughing, Necrosis & Inflammation Failure to pass meconium Abdominal Distention, Constipation Absence of ganglionic nerves in submucosal/myenteric plexi Resorption/ Sweat NaCl Pulmonary Infections (Pseudomonas) Pancreatic Insufficiency; Male Infertility Cirrhosis; Malabsorption Unexplained Death < 1 year old Agonal Petechiae Astrogliosis of brainstem

Buzzwords
Rh (D) Antigen

Other
Incompatability doesnt become problematic until second pregnancy Most Common Cause of Neonatal Respiratory Distress Syndrome Resuscitation at birthNormalRespiratory Distress in 30 min. Treated with corticosteroids (induce maturation) Risks: PDA, Retrolental Fibroplasia, Bronchopulmonary Dysplasia

Hyaline Membrane Disease

Ground Glass CXR PDA

Retrolental Fibroplasia

Hyaline Membrane/RDS O2 Vascular Endothelial Growth Factor

Bronchopulmonary Dysplasia

Very Low Birth Weight Gut Immaturity, Oral Feeding Colonization with bacteria Mucosal Injury Impaired blood flow Downs Syndrome Neurologic Defect Abnormal Migration of neural crest

Prevented using High Frequency Ventilation, Extracorporeal membrane oxygenation, Liquid Ventilation

Necrotizing Enterocolitis

Hirschsprungs Disease

Male Predominance

Cystic Fibrosis

CFTR Defect (7q31-32 F508) URIs, Prone Sleeping Position Thermal Stress, Males African American, Prematurity Maternal Smoking/Drug Abuse

F508 Elevated Sweat Chloride

Most Common Lethal Genetic Disease in White Population

Sudden Infant Death Syndrome

Child Abuse/Neglect

Shaken Baby: Subdural & CN II Hemorrhages, Posterior Fractures Battered Child: Bruises, Pattern Injury, Abdominal Trauma, Fractures of varying ages, Lacerated Frenulum Sexual Abuse: Geniral trauma, torn hymen Caregiver simulates illness in child for secondary gain Unwitnessed Events & Repeat Hospitalizations Benign Common in infancy, spontaneously regresses Associated with Tuberous Slcerosis & von Hippel Lindau Benign Usually cystic or cavernous

Munchausen Syndrome by Proxy

Hemangioma

Lymphangioma

Deep neck, axilla, mediastinum or retroperitoneal

Pediatric Pathology (contd.)

Cause/Risk Factors

Symptoms
Teeth, hair, bone, skin

Buzzwords

Other
Benign cystic to malignant solid

Sacrococcygeal Teratoma

Congenital Anomalies

Teeth, hair, bone, skin Adrenal Mudulla mass, fever, weight loss Encapsulated or infiltrative, cystic, hemorrhagic Calcified, Sheets of small blue cells Homer-Wright Pseudorosettes; Peri-orbital mets

75% mature, benign; Most common malignant tumor <1 yo Can become ganglioneuroma Bad = Diploid, del 1p, N-myc, Stage IV = Blueberry Muffin Baby Good=Stage IV-S, <1 yo, Hyperdiploid 2nd most common malignant tumor 3 cell types: Blastema (small round cells), Epithelial & Stromal Amount of Blastema = prognosis 90% long term survival

Neuroblastoma

Homer-Wright Pseudorosettes Small Blue Cells

Wilms Tumor (Nephroblastoma)

WT-1 & 2

Large palpable abdominal mass, Hematuria Intestinal obstruction, pulmonary mets Nephroblastomatosis Precursor Large, circumscribed, cystic Wilms Tumor Aniridia Genital Anomalies Retardation Gonadal Dysgenesis Wilms Tumor Hemihypertrophy, Organomegaly, Macroglossia Renal Medullar Cysts, Adrenal Cytomegaly Wilms Tumor, Other Tumors Diaphysis of long bones Sheets of small round blue tumor, glycogen

WAGR Syndrome

11p13 (aniridia) WT-1

Denys-Drash Syndrome

WT-1

Beckwith-Wiedemann Syndrome

WT-2 (11p15.5)

Other Tumors: Hepatoblastoma, Adrenocortical tumors, RMS, Pancreatic Tumors

Ewing Sarcoma

t11:22

Small Blue Cells

White male (never black) Metastatic in 25% of cases

Extraosseous Ewing Sarcoma Primitive Neuroectodermal Tumor (PNET)

t11:22

Neural differentiation Rosettes Painless, proptosis, CN palsies, chronic drainage Urinary obstruction, constipation, Hematuria Small blue cell tumor Enlarging Abdomen Fetal or Embryonal Stem Cells Leukocoria (white papillary reflex) Assymetry, Strabismus, Painful Eye Rosettes, Calcifications Most common soft tissue sarcoma of children Peak 2-5 yo & again in adolescence Good = Embryonal: Botryoid (grapes from vagina) or Spindle Cell Bad = Alveolar in extremities & trunk

Rhabdomyosarcoma

t2:13 (Alveolar)

Small Blue Cells

Hepatoblastoma

Retinoblastoma

Rb1 on Ch 13

Pediatric Pathology (Contd. 2)

Cause/Risk Factors
Household Smoking

Symptoms
Solitary, esp. bone Histiocytes & Eosinophil Infiltrate Birbeck Granules MultifocalBone Lesions, Weight Loss, Otitis Media, Exophthalmos, Diabetes Insipidus Histiocytes & Eosinophil Infiltrate Birbeck Granules Disseminated, Blood Abnormalities, Fever Seborrheic Skin Rash, Weight Loss, HSmegaly Lymphadenopathy, Histiocytes Eosinophil Infiltrate, Birbeck Granules Left to Right (Acyanotic), Eisenmenger Syndrome (Later) Poorly formed AV Valves Narrowed or Constricted Aorta 50% bicuspid aortic valve Systolic murmur (+ thrill) LVH & Cardiomegaly Right to Left (Cyanotic) No division into Aorta & Pulmonary Artery Single Vessel w/ vareiable # of cusps in valve

Buzzwords
Birbeck Granules

Other

Eosinophilic Granuloma (Langerhans Cell Histiocytosis)

Household Smoking

Birbeck Granules

Letterer-Siwe Disease (Langerhans Cell Histiocytosis)

Household Smoking

Birbeck Granules

Often Fatal Partial: Primum ASD & Cleft Anterior Mitral Leaflet, Mitral Insufficiency, Two valve orifices Complete AVSD: Large AVSD & Common AV Valve Subtypes (Rastelli A,B,C) based on bridging of anterior leaflet If with PDA, manifests early, lower body cyanosis If without PDA, less severe, upper body hypertension

Atrioventricular Septal Defect (AV Canal)

Trisomy 21 (Down Syndrome)

Coarctation of Aorta

Monosomy X (Turner Syndrome)

Truncus Arteriosus

DiGeorge (del 22q11)

Early Repair to avoid late complications

Pulmonic Stenosis

Noonan Syndrome (Chr 12q22)

RVH, Post stenotic dilation of arteries

Variable severity

Supravalvular Aortic Stenosis

Williams Syndrome (Chr 7 Elastin) Left to Right (Acyanotic), Eisenmenger Syndrome (Later) Machinery Like Murmur Assymptomatic Right to Left (Cyanotic) 1) VSD 2) Rt Ventricular Outflow Obstruction 3) Rt Ventriculare Hypertrophy 4) Overriding Aorta Right to Left (Cyanotic) Abnormal Formation of Septa Separation of Systemic/Pulmonary Circulation Right Ventricular Hypertrophy TGA with Inversion of ventricles Aorta in parallel and to left of Pulmonary Artery

Patent Ductus Arteriosus

Rubella Infection

Machinery Murmur

Treatment: Surgery or Indomethacin (PG Inhibitor)

Tetrology of Fallot

Boot Shaped Heart; VSD usually large Hypercyanotic episodes due to RVOT spasm Usually accompanied with Pulmonary Stenosis Requires shunt for survival (usually PDA) Aorta is anterior and to right of Pulmonary Artery (nl = posterior)

Transposition of Great Arteries

Corrected TGA

Late decompensation of right ventricle due to systemic demand

Pediatric Pathology (contd. 3)

Cause/Risk Factors

Symptoms
Right to Left (Cyanotic) Unequal division of AV canal, large mitral orifice RV Hypoplasia Right to Left (Cyanotic) No pulmonary veins into left atrium RA or RV hypertrophy Left to Right (Acyanotic), Eisenmenger Syndrome (Later) Pulmonary Overcirculation (Flow Murmur) Left to Right (Acyanotic), Eisenmenger Syndrome (Later) Harsh Holosystolic Murmur Cyanotic Constriction of Pulmonary Arteries, Intimal Lesions & Plexiform Lesions at branches Cor Pulmonale If severe, may cause hypoplastic left heart syndrome (HLHS) LV Hypertrophy, Systolic murmur (+ thrill) Thickened wall of ascending aorta Associated with Williams Syndrome LV Hypertrophy, Systolic murmur (+ thrill) Thickened ring below aortic cusps Usually isolated May be associated with coarctation & PDA LV Hypertrophy, Systolic murmur (+ thrill)

Buzzwords

Other
Requires a right to left shunt (ASD or PFO) as outlet from RA VSD allows outflow from Pulmonary Artery High Mortality Requires ASD or PFO to allow pulmonary blood into the left atrium RA or RV hypertrophy Secundum: Midseptal, fossa ovale, least problematic, most common Primum: Adjacent to AV Valves, Cleft Anterior Mitral Valve Leaflet Sinus Venosus Defect: Near Superior Vena Cava Usually associated with other CHD Membranous: Large, more common Muscular: Multiple, smaller, well tolerated Infundibular: Below pulmonary valve, large Ireeversible

Total Anomylous Pulmonary Veinous Return

Atrial Septal Defect

Ventricular Septal Defect

Eisenmenger Syndrome

Pulmonary Hypertension

Valvular Aortic Stenosis

HLHS: LV & arch hypolplasia; LV endocardial fibroelastosis

Supravalvular Aortic Stenosis

Chr 7q (Williams Syndrome)

Williams Syndrome: Facies, Cocktail Personality, MR

Subvalvular Aortic Stenosis

Cardiac Pathology
Disease
Atherosclerosis

Cause/Risk Factors
Atheromas at Branch Points LDL, HT, Smoking, DM, Fam Hx Fatty Streaks? Atherosclerosis Ulceration

Symptoms
Medium & Large Arteries Foam Cells (Macrophage & Smooth Muscle)

Buzzwords
Foam Cells Intima

Other
Located in intima Consists of a fatty core covered by a fibrous cap & endothelium Exposed Rough Surface allows attachment of platelets and fibrin May embolize (thromboembolism) Can cause sudden occlusion Main cause of myocardial infarcts Disintegration of the fibrous cap with release into bloodstream May allow for formation of thrombus within the plaque Can cause sudden occlusion Crack in cap allows blood in or neovessels within plaque may burst Can cause sudden occlusion May cause infarcts

Atherothrombotic Erosion (Atherothrombosis)

Mural Thrombosis

Atherothrombotic Rupture

Atherosclerosis

Atheromatous Embolus

Atherosclerotic Hemorrhage

Atherosclerotic Calcification

Brittle Arteries

Hardening of arteries with time Enlarged plaque compresses media layer (pressure atrophy) Causes ballooning (aneurysm) Focal area of wall = saccular aneurysm Circumferential Involvement = Fusiform aneurysm If thrombosis is complete it may cause necrosis of the toe or foot Rapidly spreading intramural hemorrhage Creates a second lumen in the media layer Initial intimal tear accompanied by a distal reentry tear May compress the aortic valve & cause insufficiency Located opposite the ligamentum arteriosum Lower half of the body is supplied by collaterals Associated with a bicuspid valve

Atherosclerotic Degeneration

Aneurysm

Intermittent Claudication

Atherosclerosis in Femoral Artery Atherosclerosis in Popliteal Artery Hypertension Cystic Medial Necrosis Marfans Syndrome Pregnancy, Coarctation of the Aorta Congenital Turners Syndrome

Walking pain

Acute Aortic Dissection

Chest Pain Hypotension Pericardial Tamponade Proximal Hypertension/Distal Hypotension CHF Rib notching on CXR

Chest Pain Tamponade Compressed Aortic Valve Rib Notching Bicuspid Valve Granulomatous Age > 50 Large Arteries Cranial Arteries Destruction of IEL Granulomatous Age < 40 & often Female Aortic Narrowing; Weak pulses Extremities Medium Sized Arteries (not lungs) No Glomerulonephritis Dilated Aneurysms

Coarctation of the Aorta

Giant Cell Arteritis

Takayusus Arteritis

Polyarteritis Nodosa

Many organs

Cardiac Pathology (contd)

Cause/Risk Factors

Symptoms

Buzzwords
Large & Medium Sized Arteries Children Coronary Arteries Aneurysms Small Vessels Glomerulonephritis No Immune Deposits Small Vessels Granulomas in Lungs Granulomatous Vasculitis Renal Disease Medium & Small Arteries Heavy Smokers Extremities Microabscesses

Other
Infantile Polyarteritis

Hypersensitivity Angitis

All organs

Wegeners Arteritis

Buergers Arteritis Poor Tissue Perfusion/Venous Backup (Edema) Tachycardia; Angiotensin II Pre-renal Azotemia; Ischemic Colitis Liver Necrosis, Muscle Wasting; Lung Edema Assymptomatic (Diabetes) Arrythmias, Mitral Insufficiency Pericardial Tamponade, Aneurysm, Thrombus Pericarditis Pain with exertion

Congestive Heart Failure

Many Chronic Ischemia & Inflammation Atherosclerosis; Arterial Spasm Hypotension Aortic Valve Disease: (Syphilis, Polyarteritis, Kawasaki) Exertion (Relieved by Rest) Stenosis

Hemosideran Laden Macrophages Cardiogenic Shock occurs w/ loss of > 40% of left ventricle function

Ischemic Heart Diseaes

Right Coronary Artery: Posterior LV & AV Node Left Anterior Descending: Anterior LV &AV Node Left Circumflex: Lateral LV & Papillary Muscles

Stable Angina Pectoris

Reversible Ischemic Injury

Atypical Angina (Prinzmetals)

Spasm

Pain at rest (spontaneous reduction in supply) Troponin (1st), CK (later) ST ,Q Waves, Loss of R Waves, Arrhthmias Leukocytosis, SR Pain(Squeezing), Radiation, Diaphoresis, N&V Arthritis, Rash, Nodules & Chorea B Cell Alloantigens Verrucae on Vavles (Mitral Stenosis) Aschofff Bodies (no organisms) Diastolic Murmur with opening snap Fishmouth appearance Atrial Fibrillation Subendocardial: Transmural: Full thickness of wall, more common Troponin I & T are gold standard sensitivity (elevated for days) LDH1>LDH2 after 24 hours Pancarditis (Bread & Butter), Myocarditis, Endocarditis

Myocardial Infarction

Underperfusion Severe atherosclerotic narrowing

Rheumatic Heart Disease

Genetic? Group A Strep

Mitral Stensosis

Rheumatic Fever (Disease) Young Females

Mitral Prolapse

Marfans Syndrome Post MI LV Dilation

Late Systolic Murmur with Midsystolic click

Can cause CHF, Arrhythmias, Sudden death & endocarditis

Cardiac Pathology (contd 2)

Cause/Risk Factors
Diseased Valves Congenital Defects IV Drug Use

Symptoms
Fever, Splinter Hemorrhages, Oslers Nodes Heart Failure, Hemiplegia, Changing Murmur Anemia, Hematuria, + Culture

Buzzwords

Other
Staph, Pneumonia & Gonococcus are especially destructive Biggest problem is septic emboli

Valve Replacement

Fen-Phen

Porcine: 5-10 year durability Mechanical: Requires anti-coagulation; concern for hemolysis

Cardiac Myxoma Renovascular, Chronic Renal Disease, Hyperaldosteronism, Cushings Pheochromocytoma, Coarctation Estrogens, Alcohol, Amphetamines Primary: Idiopathic Secondary: Alcohol, DMD Viral (Coxsackie B3), Genetic?, Drugs (Adriamycin), Primary: Idiopathic Secondary: Amyloidosis, Hemochromatosis (Thalessemia) Sarcoidosis, Glyc. Storage Disease Primary: Idiopathic Secondary: Genetic (B Myosin, Tropomyosin, Troponin) (Myosin Binding Protein C: older pts)

Usually benign Polypoid, pedunculated, extends into chamber

Hypertension

Normal <120/80; Pre <130/90; Stage I <160/100 Subintimal fibrosis & hyalinization Dilation of all 4 chambers DOE/Rest, Weakness, HSmegaly Risk of thromboemboli/infarction Death within 5 years without transplant Dilated Atria Low Voltage on ECG Young People Profound IVS/LV Hypertrophy Systolic Murmur Q Waves

Essential Hypertension is the majority and has no known cause Estrogens are the most common reversible cause (OCT)

Dilated Cardiomyopathy

Restrictive Cardiomyopathy

Decreased compliance (like constrictive pericarditis) Decreased LV Volume/Mitral Valve Insufficiency/Obstruction Sub-aortic Stenosis Prone to arrythmias & CHF Better prognosis than dilated cardiomyopathy

Hypertrophic Cardiomyopathy (IHSS)

Blood Pathology
Disease
Anisocytosis

Cause/Risk Factors
Sideroblastic Anemia

Symptoms
Variation in size Increased RDW Small Cells Low MCV Hypochromic Large Cells High MCV Decreased hemoglobin Increased zone of central pallor Usually microcytic Increased Hemoglobin Increased MCHC

Buzzwords

Other

Microcytosis

Iron Deficiency Anemia Thalassemia Folate & B12 Deficiencies Alcoholism Hypothyroidism Post Chemotherapy Iron Deficiency Anemia Thalassemia

Macrocytosis

Hypochromia

Hyperchromasia

Spehrocytosis

Polychromasia

Henolysis Blood Loss

Blue Reticulocytes (Wrights Stain) Basophilic stippling in reticulocytes

Ovalocyte (Poikilocytosis)

Normal (< 10% of blood) B12 & Folate Deficiency Normal (< 10% of blood) Heriditary Elliptocytosis Iron Deficiency, Thalassemia Hemoglobinopathies Thalassemia Hemoglobinopathies Iron Deficiency Obstructive Liver Disease Splenectomy Heriditary Spherocytosis Warm antibody immune hemolysis Fibrin Strand Damage Heart Valve Replacements Microangiopathic Hemolytic Anemia DIC, Burns Hyperosomolarity Renal Failure

Variation in shape = oval

Elliptoocyte (Poikilocytosis)

Variation in shape = elliptical

Target Cells

Liver Disease causes lipid metabolism abnormalities

Spherocytes

Lack biconcave shape & central pallor Increased MCHC

Defect in internal support proteins in hereditary condition

Schistocytes

Cell fragments

AKA Helmet Cells

Echinocytes

Irregular Margin Bumpy surface

Blood Pathology (contd)

Cause/Risk Factors
Liver Disease Abetalipoproteinemia Post-SPlenectomy Myeloproliferative Disease Megaloblastic Anemia Thalassemia Hemoglobin S Decreased O2 or pH Splenectomy Megaloblastic Anemia Abnormal Erythropoeisis Hemolytic Anemia G6PD Deficiency Toxin Damage

Symptoms
Spicules with bulbous ends

Buzzwords

Other

Dacrocytes (Teardrop cells)

Teardrop shape

Drepanocytes (Sickle Cells)

Howell-Jolly Bodies

Remnants of nuclear chromatin Single Marginal Clump

Heinz Bodies

Fragments of denatured hemoglobin Single Marginal Clump

Basophilic Stippling

Lead Poisoning Thalassemia Excess Iron Splenectomy Sideroblastic Anemias Erythroblastosis Fatalis Space Occupying Marrow Lesions

Pappenheimer Bodies

Normoblasts

Normal in newborn

Rouleaux Formation

Multiple Myeloma

Increased Plasma Protein

Blackfan Diamond Syndrome

Pure Red Cell Aplasia

Bernard-Soulier Syndrome

Genetic (AD)

Bleeding Tendency Large platelets with thrombocytopenia

Deficiency of GP Ib Receptors

Glanzmanns Thrombasthenia

Genetic (AD)

Absence of platelet aggregation Minimal Bruising to Severe Hemorrhage

Deficiency of GP IIb/IIIa Receptors

Blood Pathology (contd 2)

Cause/Risk Factors
Genetic

Symptoms
Mild to moderate bleeding diathesis Impaired aggregation

Buzzwords

Other
Deficiency of Dense Granules (ADP & Serotonin) More Common Type APTT of 50-65 sec = moderate Rx: 1 unit of VIII = 2% increase for 11 hours (minimal = 30%) Can also use Desmopressin, E-Aminocaproic and Tranexamic Acid Rx: 1 unit of IX = 1% increase for 22 hours (minimal = 30%)

Hemophilia A (Classical Hemophilia)

Favtor VIII Deficiency (X-Linked) Mutation (30%)

Intrinsic Pathway Deficiency Abnormal APTT 20% develop IgG4 antibodies

Hemophilia B (Christmas Disease)

Favtor IX Deficiency (X-Linked) Mutation (30%)

Intrinsic Pathway Deficiency Abnormal APTT 20% develop IgG4 antibodies Muco-cutaneous bleeding VWF activity & antigen Factor VIII No HMW VWF Moderate Factor VIII & VWF Antigen Severe VWF Activity Bleeding from defect in 1 Hemostasis No HMW VWF Grossly abnormal PFA-100 test Moderate VWF Activity & Antigen Normal VWF lefels Normal level of Factor VIII Mimics Mild Hemophilia A Facotr VIII levels of ~10% Normal levels of VWF Abnormal PFA-100 Prolonged APTT due to VIII Bleeding from mucous membranes Bleeding into muscles & joints Variable Assymptomatic to Transfusions Required

Type 1 Von Willebrand Disease

Genetic (AD low penetrance)

Type 2a Von Willebrand Disease

Genetic (AD)

Impaired polymerization & cytoplasmic retention or degradation

Type 2b Von Willebrand Disease

Genetic (AD)

Increased affinity of HMW VWF to GP1b receptors & clearance Increased affinity of platelets for ristocetin (VEF:RCof)

Type 2M Von Willebrand Disease

Decreased platelet directed function of VWF

Type 2N Von Willebrand Disease

Genetic (AR)

Decreased affinity of VWF for Factor VIII Inability of VWF to bind and stabilize Factor VIII

Type 3 Von Willebrand Disease

Genetic (AR)

Absent VWF synthesis in megakaryocytes & endothelium

Factor XI Deficiency

Ashkenazi Jews

Prophylactic transfusions with antifibrinolytic therapy for surgery

Factor XIII Deficiency

Severe Bleeding Early in life Normal coagulation tests

Treat with plasma or cryo t1/2 of Factor XIII is ~ 8 days & prevents bleeding at 1% notmal

Afibrinogenemia

Genetic (AR)

Intermittant Hemorrhage PT, APTT, TCT all prolonged

Rx: Cryo

Blood Pathology (contd 3)

Cause/Risk Factors
Genetic (AD)

Symptoms
Majority are assymptomatic Abnormally functioning fibrinogen Coagulation tests prolonged Antibodies to Factor VIII Similar to Hemophilia A

Buzzwords

Other
Fibrinogen doesnt convert to fibrin

Aquired Hemophilia

Autoimmune

Rx: Immunosuppression

Aquired Type 3 VWD

Autoimmune

Antibodies to VWF

Rapid Clearance of VWF Rx: Desmopressin (release of VEF from stores)

Venous Thrombosis

1) Stasis 2) Endothelial Damage 3) Hypercoaguable State

May cause Edema & congestion, Infarction or Embolization

Outcomes: Propagation, Embolization, Dissolution, Organization, Recanalization

White Infarct

Solid Tissue: Heart, Kidney, Spleen, etc Wedge Shaped

Tissue is so dense that hemorrhage is minimal Result from arterial occlusion

Red Infarct

Hemorrhagic Wedge Shaped

Tissues where bleeding is profuse

Septic Infarcts Obstetric Complications (most) Infection Neoplasia Massive Tissue Injury Genetic (AD) Pregnancy, Surgery, Trauma, Infection

Abscess Formation Microangiopathic Hemolytic Anemia Low platelets & coagulative factors (PT & PTT) Infarction Petichiae, Ecchymoses & Oozing Thromboembolism (Types 1,2 & Homozygous 3) Juvenile onset with thrombosis in unusual sites

Usually bacterial and embolic from valve vegetations

Disseminated Intravascular Coagulation (DIC)

Ooozing

Activation of coagulation casecade with microthrombi Consumptive Coagulopathy Activation of fibrolytic pathway ( D DImers) Type 1: Absence of protein synthesis Type 2: Defect in enzyme binding domain Type 3: Defect in heparin binding domain Rx: Oral Anticoagulants Protein C is normally activated by Thrombomodulin/Thrombin APC normally cleaves VIIIa & Va Heterozygous patients at no increased risk Rx: Recombinant Protein C

Heriditary Deficiency of AT

Heriditary Deficiency of Protein C

Genetic (AR)

Neonatal Purpura Fulminans DIC

Heriditary Deficiency of Protein S

Genetic (AD)

Thrombosis

Carriers at risk

Two Types: 1) Free & Bound Reduced 2) Free Reduced Carriers at risk

Factor V Leiden Mutation

Genetic (AD)

Decreased Sensitivity of Factor V to APC Thrombosis

Replacement of Arginine by Glutamine

Blood Pathology (contd 4)

Cause/Risk Factors

Symptoms
Increased level of prothrombin activity Risk for venous thromboembolism Anemia, Hyperbilirubinemia, Siderosis Reticulocytosis, HSmegaly, PE, Priapism Fever, Pain Spiky head XRay Benign Hematuria Crisis with extreme hypoxia Mild Hemolytic Anemia Abdominal Pain Splenomegaly & Jaundice Benign & Assymptomatic Slight HbA2 & HbF elevations

Buzzwords

Other
Guanine to Adenine mutation in 3 UTR of Prothrombin gene

Sickle Cell Disease

Genetic (AR) Homozygous Hemoglobin S

HbSS

Sickle Cell Trait

Genetic (AR) Heterozygous Hemoglobin S

HbAS

Homozygous Hemoglobin C

Genetic (AR)

HbCC

Heterozygous Hemoglobin C

HBAC

Hemoglobin SC Disease

Similar to Sickle Cell Disease (less severe) Severe anemia in infancy Splenic Enlargement, Iron Overload, Early Death Anisocytosis, Poikilocytosis, Microcytosis, Hypochromia, Target Cells & Polychromatophilia Moderate anemia Thalassemic morphology

Thalassemia Major

Requires lifelong blood transfusions

Thalassemia Intermedia

Thalassemia Minor

No anemia or mild anemia Thalassemic morphology

Thalassemia Minima

Normal Detected only by family studies