Hematology and Oncology Pathology

Acanthocyte (spur cell)

• Associated Pathology:
• -liver disease
• -abetalipoproteinemia (state of XOL dysregulation)

Basophilic Stippling

• Associated Pathology:
• -Thalassemias
• -Anemia of chronic disease
• -Lead poisoning

"Baste the ox TAiL"

Bite Cell

• Associated Pathology:
• -G6PD deficiency

Elliptocyte

• Associated Pathology:
• -hereditary elliptocytosis

Ovalocyte (Macro-ovalocyte)

• Associated Pathology:
• -Megaloblastic anemia
• -marrow failure

Ringed Sideroblast

• Associated Pathology:
• -Sideroblastic anemia
• -excess iron in mitochondria = pathologic

• Schistocyte
• Helmet Cell

• Associated Pathology:
• -DIC
• -TTP/HUS
• -traumatic hemolysis (prosthetic heart valve)

Sickle Cell

• Associated Pathology:
• -sickle cell anemia

Spherocyte

• Associated Pathology:
• -Hereditary spherocytosis
• -Autoimmune hemolysis

Teardrop cell

• Associated Pathology:
• -Bone marrow infiltration (eg: myelofibrosis)

"RBC sheds a tear because it's been forced out of its home in the bone marrow"

Target Cell

• Associated Pathology:
• -HbC disease
• -Asplenia
• -Liver disease
• -Thalassemia

"HALT" said the hunter to his target

Heinz Bodies

• Associated Pathology:
• -G6PD deficiency
• -similar inclusion seen in α-thalassemia

• Pathophysiology:
• -oxidation of iron from ferrous to ferric form leads to denatured hemoglobin precipitation and damage to RBC membrane

Howell-Jolly Body

• Associated Pathology:
• -Functional hyposplenia
• -asplenia
• -mothball ingestion (naphthalene)

• Pathophysiology:
• -basophilic nuclear remnants
• -normally removed from RBCs by splenic MPs

Reduction in circulating RBC mass

• Presentation: sx of hypoxia
• 1. Weakness, fatigue, dyspnea
• 2. Pale conjunctiva and skin
• 3. Headache and lightheadedness
• 4. Angina

• Hemoglobin (Hb), hematocrit (Hct), and RBC count are surrogates for RBC mass. 
• -Male: Hb < 13.5g/dL
• -Female: Hb < 12.5 g/dL
• 
  -Microcytic: MCV <80
• -Normocytic: MCV between 80 and 100
• -Macrocytic: MCV >100

"Puny TICS"

• -Pernicious anemia
• -Thalassemia
• -Iron deficiency anemia
• -Chronic disease (anemia of chronic disease)
• -Sideroblastic anemia
• *Lead Poisoning

• Due to decreased production of hemoglobin
• RBC progenitors (erythroblasts) go through an "extra" division to maintain hemoglobin concentration

• -Hemoglobin = heme + goblin
• -Heme = iron + protoporphyrin

• Epidemiology:
• -most common type of anemia

• Etiology:
• -chronic bleeding (GI loss, menorrhagia)
• -increased demand (pregnancy)
• -malnutrition/absorption disorders (gastrectomy: acid needed to absorb Fe²⁺)
• "Fe²⁺ goes in2 the body"

• Pathophysiology:
• -↓Iron → ↓heme → ↓hemoglobin → microcytic anemia

• Presentation:
• -anemia
• -koilonychia (spoon-shaped nails)
• -pica

• Labs:
• -microcytic, hypochromic RBCs, ↑RDW
• -↓ iron
• -↑ TIBC
• -↓ ferritin
• -↓ % saturation

1. Iron is absorbed in the duodenum

2. Enterocytes transport iron into the blood via ferroportin

3. Transferrin transports iron in the blood and delivers it to liver and BM MPs for storage

4. Stored intracellular iron is bound to ferritin (prevents iron from undergoing the Fenton reaction and forming free radical)

• Serum Iron:
• -iron in the blood

• TIBC:
• -measure of transferrin molecules in the blood
• -transferrin carries Fe in the blood

• % Saturation:
• -percentage of transferrin molecules that are bound by iron (normal 33%)

• Serum Ferritin:
• -measures iron stores in MPs and liver

• 1. Stored iron is depleted
• -↓ ferritin
• -↑ TIBC

• 2. Serum iron is depleted
• -↓ serum iron
• -↓ % saturation

• 3. Normocytic anemia
• -BM makes fewer, but normal-sized RBCs

• 4. Microcytic, hypochromic anemia
• -BM makes fewer and smaller RBCs

• Epidemiology:
• -cis deletion → Asian
• -trans deletion → African
• -inherited mutations that cause decreased synthesis of α globin chains
• *protective against malaria

• Pathophysiology:
• -four alpha genes present on chromosome 16
• -microcytic anemia

• 4 gene deletion:
• -not compatible with life → causes hydrops fetalis
• -hemoglobin γ4 forms (Hb bart)

• 3 gene deletion:
• -very little α-globin
• -β-chains form tetramers (HbH) that damage RBCs
• -severe anemia

• 2 gene deletion:
• -mild anemia (not clinically significant) with increased RBC count
• -cis deletion has higher risk of severe thalassemia in offspring

• 1 gene deletion:
• -no clinically significant anemia

• Epidemiology:
• -prevalent in Mediterranean population

• Pathophysiology:
• -point mutations in splice sites and promoter sequence cause ↓ β-globin synthesis
• -β⁰ = absent
• -β⁺ = diminished production

• Labs:
• -microcytic, hypochromic RBCs
• -target cells
• -increased HbF and HbA₂ (α₂δ₂)

• β-Thalassemia Minor (heterozygous)
• -β/β⁺
• -underproduction of β chain
• -usually asymptomatic
• -increased HbA2 on electrophoresis

• β-Thalassemia Major:
• -β⁰/β⁰
• -absent β chain
• -severe anemia
• -α tetramers aggregate and damage RBCs (cleared by spleen)
• -tx: frequent transfusions (2° hemochromatosis)
• -marrow expansion ("crew cut" on skull x-ray/"chipmunk" facies)
• -increased HbF

**risk of aplastic crisis with parvo B19 infection

• HbS/β-Thalassemia Heterozygote:
• -mild to moderate sickle cell disease
• -depends on amount of β-globin production

• Pathophysiology:
• -lead inhibits ferrochelastase and ALA dehydratase → ↓ heme synthesis
• -inhibits rRNA degradation, causing RBCs to retain aggregates of rRNA (basophilic stippling)
• -high risk in houses with chipped paint

• "LEAD"
• Lead Lines gingivae (Burton's lines) and on metaphyses of long bones on x-ray
• Encephalopathy and Erythrocyte basophilic stippling
• Abdominal colic and sideroblastic Anemia
• Drops: wrist and foot drop. Dimercaprol and EDTA are first line treatment

Succimer used for chelation for kids ("It sucks to be a kid who eats lead")

• Pathophysiology:
• -defect in protoporphyrin synthesis
• -iron builds up in mitochondria (ringed sideroblasts)

• Etiologies:
• 1. Congenital
• -X-linked defect in δ-ALA synthase gene

• 2. Acquired
• -alcohol (mitochondrial poison)
• -lead poisoning
• -isoniazid (B6 deficiency)

• Lab Findings:
• -↑ iron
• -normal TIBC
• -↑ ferritin
• (iron overloaded state)

• Epidemiology:
• -Most common type of anemia in hospitalized patients

• Pathophysiology:
• -inflammation → ↑ hepcidin (acute phase reactant released by liver)
• -hepcidin binds ferroportin on MP and mucosal cells and inhibits iron transport
• -hepcidin also suppresses EPO

• Lab Findings:
• -↓ iron
• -↓ TIBC
• -↑ ferritin
• -anemia can be microcytic or normocytic

• Treatment:
• -treat underlying cause
• -exogenous EPO can be useful in pts with cancer

• 1. MEGALOBLASTIC
• -Folate deficiency
• -B12 deficiency
• -Orotic aciduria

• 2. NON-MEGALOBLASTIC
• -Liver disease
• -Alcoholism
• -Reticulocyte

Impaired DNA synthesis → maturation of nucleus delayed relative to maturation of cytoplasm

Impaired division of granulocytic precurors leads to hypersegmented neutrophils

Ineffective erythropoiesis → pancytopenia

• Causes:
• -Folate deficiency
• -B12 deficiency

• Etiologies:
• -malnutrition (alcoholics)
• -malabsorption
• -antifolates (methotrexate, TMP, phenytoin)
• -↑ requirement (hemolytic anemia, pregnancy)

• Pathophysiology:
• -dietary folate from green veggies is absorbed in the jejunum
• -deficiency develops within months (minimal body stores)

• Lab Findings:
• -macrocytic anemia
• -hypersegmented neutrophils
• -glossitis
• -↓ folate
• -↑ homocysteine (risk of thrombosis)
• -NORMAL MMA
• -NO NEUROLOGIC SYMPTOMS

• Etiologies:
• -insufficient intact (strict vegans)
• -malabsorption (Crohn's)
• -pernicious anemia
• -Diphyllobaothrium latum (fish tapeworm)
• -PPIs

• Lab Findings:
• -hypersegmented neutrophils
• -glossitis
• -↓ B12
• -↑ Homocysteine
• -↑ MMA

• Neurologic Symptoms:
• -subacute combined degeneration (B12 important for FA and myelin synthesis)
• -peripheral neuropathy with sensorimotor dysfunction
• -Posterior colums
• -Lateral cotricospinal (spasticity)
• -Dementia

1. B12 from animal derived proteins is liberated by amylase

2. B12 is bound to R-binder than carried to the stomach

3. Pancreatic proteases in the duodenum detach B12 from R-binder

4. Vitamin B12 binds intrinsic factor

5. B12-Intrinsic factor complex is absorbed in the ileum

• Pathophysiology:
• -genetic mutation in enzyme that synthesizes uridine from orotic acid

• Presentation:
• -megaloblastic anemia in children that cannot be cured with folate/B12
• -hypersegmented neutrophils
• -glossitis
• -orotic acid in urine

• Treatment:
• -uridine monophosphate to bypass mutated enzyme

• Pathophysiology:
• -DNA synthesis is unimpaired

• Causes:
• -liver disease
• -alcoholism
• -reticulocytosis (increased MCV)
• -drugs (5FU, AZT, hydroxyurea)

Macrocytosis and BM suppression can occur in the absence of folate/B12 deficiency

• 1. NON-HEMOLYTIC
• -ACD
• -Aplastic Anemia
• -Chronic Kidney Disease

• 2. HEMOLYTIC
• A) INTRINSIC
• -Hereditary Spherocytosis
• -G6PD deficiency
• -PK deficiency
• -HbC
• -SCA
• -Paroxysmal nocturnal hemoglobinuria

• B) EXTRINSIC
• -Autoimmune
• -Microangiopathic
• -Macroangiopathic
• -Infections

• Pathophysiology:
• -destruction of RBCs within vessels

• Findings:
• -↓ Haptoglobin
• -↑ LDH
• -Hb in urine

• Pathophysiology:
• -destruction or RBCs by reticuloendothelial system (MPs of spleen, liver and LNs)

• Findings:
• -splenomegaly
• -↑ UCB: jaundice
• -↑ LDH

• Anemia of Chronic Disease
• Aplastic Anemia
• Chronic Kidney Disease

• Pathophysiology:
• -failure or destruction of myeloid stem cells

• Etiology:
• -radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites)
• -Viral agents (Parvo B19, EBV, HIV, HCV)
• -Fanconi's anemia (DNA repair defect)
• -Idiopathic (immune mediated, primary stem cell defect, may follow acute hepatitis)

• Findings:
• -pancytopenia
• -normal cellular morphology
• -BM bx: hypocellular BM with fatty infiltrate

• Presentation:
• -fatigue
• -malaise
• -pallor
• -purpura
• -mucosal bleeding
• -petechiae
• -infection

• Treatment:
• -withdraw offending agent
• -immunosuppressive regimen (antithymocyte globulin, cyclosporine)
• -allogeneic bone marrow transplant
• -RBC and platelet transfusion
• -G-CSF, GM-CSF

Decreased EPO → decreased hematopoiesis

• Pathophysiology:
• -acquired mutation in HSC
• -defect in GPI anchor
• -GPI anchors DAF to RBC membrane
• -protects from destruction by C3 convertase
• -intravascular hemolysis
• -nocturnal: mild respiratory acidosis (activates C')
• -hemolysis of RBCs, WBC, Plts

• Presentation: PNH Triad:
• -hemolytic anemia
• -pancytopenia
• -venous thrombosis

• Labs:
• -CD55(DAF)/59 negative RBCs on flow cytometry
• -sucrose test

• Complications:
• -iron deficiency anemia
• -AML (10%)

• Treatment:
• -eculizumab (inhibit C')

• Pathophysiology:
• -X-linked recessive
• -defect in G6PD
• -decreases amount of glutathione → ↑ RBC susceptibility to oxidant stress
• -glutathione (antioxidant, NADPH from G6PD used to regenerate reduced glutathione)
• -hemolytic anemia triggered by oxidative stress (sulfa drugs, infections, fava beans)
• -intravascular and extravascular hemolysis

• Findings:
• -back pain (Hb is nephrotic)
• -hemoglobinuria a few days later
• -RBCs with Heinz bodies and bite cells

• Etiology:
• -inherited defect of RBC cytoskeleton-membrane tethering protein
• -ankyrin, spectrin, band 3, protein 4.2
• -membrane blebs are formed and lost overtime → spherocytes
• -premature removal of RBCs by spleen
• -extravascular hemolysis

• Findings:
• -spherocytes (small, round RBCs with no central power)
• -↑ MCHC
• -↑ RDW
• -splenomegaly
• -aplastic crisis with Parvo B19
• -positive osmotic fragility test (hypotonic soln)
• -abundance of cells with normal to ↓ MCV (masks microcytosis)
• -jaundice, increased risk of bilirubin gallstones (hemolysis)

• Treatment:
• -splenectomy

• Pathophysiology:
• -autosomal recessive
• -defect in pyruvate kinase leads to decreased ATP production
• -decreased ATP causes rigid RBCs

• Presentation:
• -extravascular hemolysis
• -hemolytic anemia in a newborn

• Pathophysiology:
• -autosomal recessive defect in β-globin gene
• -glutamate replaced by lysine
• "HbC has lyCine"

• Presentation:
• -mild anemia due to extravascular hemolysis
• -HbC crystals seen in RBCs

**HbSC (heterozygous for HbC and HbS) have milder disease than HbSS patients

• Epidemiology:
• -gene carried by 8% of African American (HbS trait)
• -protective against malaria

• Pathophysiology:
• -HbS mutation causes a single AA replacement in β globin (disease in homozygotes)
• -low O2 or dehydration causes HbS to polymerize → aggregate into needle like structures
• -cells continuously sickle and desickle while passing through the microcirculation
• -newborns initially asymptomatic (HbF)
• -extravascular hemolysis

• Findings:
• -sickle cells and target cells on blood smear
• -extramedullary hematopoiesis
• -"crew cut" on skull xray
• -"chipmunk" facies

• Complications:
• -caused by irreversible sickling and vaso-occlusion

• Aplastic crisis
• -parvo B19 infection

• Autosplenectomy
• -Howell Jolly bodies
• -increased risk of infection with encapsulated organisms
• -functional splenic dysfunction occurs in early childhood

• Splenic Sequestration Crisis:
• -acute painful enlargement of spleen with cell trapping

Salmonella Osteomyelitis

• Painful Crisis:
• -vaso-occlusive crisis

• Dactylitis
• -painful hand swelling (vaso-occlusive infarcts in bones)
• -common presenting sign in infants

• Acute Chest Syndrome:
• -vaso-occlusion in pulmonary circulation
• -most common cause of death in adult patients

• Renal Papillary Necrosis:
• -gross hematuria
• -proteinuria

• Pathophysiology:
• -one copy of HbS gene
• -<50% HbS in RBCs

• Presentation:
• -generally asymptomatic (no anemia)
• -can see sickling in renal medulla → microscopic hematuria

• Lab Findings:
• -no sickle cells or target cells
• -metabisulfite screen: causes cells with any HbS to sickle
• -Hb electrophoresis: 55% HbA in trait (none in Sickle cell)

• Pathophysiology:
• -antibody mediated destruction of RBCs
• -many are idiopathic in etiology

• Warm Agglutinin:
• -IgG binds RBCs in warm temperature of central body
• -membrane of Ab-coated RBCs consumed by splenic MPs → spherocytes (extravascular hemolysis)
• -chronic anemia
• -associated with: SLE, CLL, drugs (PCNs, cephalosporins)
• -tx: steroids, IVIg (distract MPs), splenectomy (remove cause of Abs and hemolysis)
• "warm weather is GGGreat"

• Cold Agglutinin:
• -IgM binds RBCs and fixes complements in the colder temperature of the extremities (intravascular hemolysis)
• -associated with: CLL, mycoplasma pneumonia or infectious mononucleosis
• "Cold ice cream -- yuMMM"

• Findings:
• -usually Coombs' positive

• -Tests for anti-body coated RBCs
• -anti-Ig antibody added to patient's serum
• -RBCs agglutinate if RBCs are coated with IgE

*most important test for IHA

• -Tests for antibodies in patient serum
• -Normal RBCs added to patient's serum
• -agglutinate if serum has anti-RBC surface Ig

• Pathophysiology:
• -RBCs damaged when passing through obstructed or narrow vessel lumina
• -intravascular hemolysis

• Etiologies:
• -DIC
• -TTP-HUS
• -SLE
• -Malignant hypertension

• Findings:
• -iron deficiency anemia with chronic hemolysis
• -schistocytes (helmet cells)

• Pathophysiology:
• -hemolytic anemia secondary to mechanical destruction

• Etiology:
• -prosthetic heart valves
• -aortic stenosis

• Findings:
• -schistocytes

• Decreased TIBC in ACD: prevent pathogens from acquiring iron

Increased transferrin production in pregnancy/OCPs

-hereditary or acquired conditions of defective heme synthesis

-lead to accumulation of heme precursors

**lead inhibits specific enzymes needed in heme synthesis → similar condition to porphyria

• Rate Limiting Step:
• -ALA synthase
• -heme and glucose inhibit

• Exposure:
• -Children: lead pain
• -Adults: environmental (battery/ammunition/radiator factory)

• Affected enzyme:
• -ferrochelatase
• -ALA dehydratase

• Accumulated substrate:
• -protoporphyrin
• -δ-ALA

• Presentation:
• -Microcytic anemia
• -GI and kidney disease
• -Children: mental deterioration
• -Adults: HA, memory loss, demyelination

• Affected Enzyme:
• -Porphobilinogen deaminase

• Accumulated Substrate:
• -Porphobilinogen
• -δ-ALA
• -uroporphyrin (in urine)

• Presentation (5 P's):
• -Painful abdomen
• -Port wine colored urine
• -Polyneuropathy
• -Psychological distrubances
• -Precipitated by drugs

• Treatment:
• -glucose and heme (inhibit ALA synthase)

• Affected Enzyme:
• -Uroporphyrinogen decarboxylase

• Accumulated Substrate:
• -Uroporphyrin (tea-colored urine)

• Presentation:
• -blistering cutaneous photosensitivity
• -most common porphyria

-tests the function of common and extrinsic pathway

-factors: I, II, V, VII and X

Defect: increased PT

-tests the function of common and intrinsic pathway

-Factors: all except VII and XIII

Defect: increased PTT

• -Hemophilia A
• -Hemophilia B
• -Vitamin K deficiency

• Pathophysiology:
• -genetic factor VIII deficiency
• -X-linked recessive
• -de novo mutation (not uncommon)
• -defect in intrinsic pathway

• Presentation:
• -macrohemorrhage
• -deep tissue, joint (hemarthroses) and postsurgical bleeding
• -easy bruising

• Labs:
• -↑ PTT
• -normal PT
• -normal platelet count
• -normal bleeding time

• Treatment:
• -recombinant factor VIII

"hemophilia 8"

• Pathophysiology:
• -genetic factor IX deficiency

• Presentation:
• -resembles hemophilia A

• Labs:
• -↑ PTT
• -normal PT
• -normal platelet count
• -normal bleeding time

• Pathophysiology:
• -disrupts function of multiple coagulation factors
• -decreased synthesis of factors: II, VII, IX, X, prot C and S
• -defect in intrinsic and extrinsic pathway

• Etiology:
• -newborns (lack of GI colonization)
• -long term abx
• -malabsorption (deficiency of fat soluble vitamins)

• Labs:
• -↑ PT
• -↑ PTT

• Disorders:
• -Bernard Soulier Syndrome
• -Glanzmann's Thrombasthenia
• -Idiopathic Thrombocytopenic purpura (ITP)
• -Thrombotic Thrombocytopenic purpura (TTP)

• Presentations:
• -↑ bleeding time
• -microhemorrhage
• -mucous membrane bleeding
• -epistaxis
• -petechiae
• -purpura

• Pathophysiology:
• -genetic GpIb deficiency
• -impaired platelet adhesion (GpIb on platelet binds vWF)
• -platelets don't live as long → thrombocytopenia

• Labs:
• -↓ platelet count
• -↑ bleeding time

• Pathophysiology:
• -genetic GpIIb/IIIa deficiency (defect in platelet-to-platelet binding)
• -impaired platelet aggregation

• Labs:
• -no platelet clumping
• -no change in platelet count
• -↑ bleeding time

• Pathophysiology:
• -anti-GpIIb/IIIa antibodies
• -causes splenic MP consumption of platelet/antibody complex

• Acute ITP:
• -children, weeks after viral infection or immunization
• -self limited
• -resolves in weeks

• Chronic ITP:
• -usually women of child-bearing age
• -primary
• -secondary (SLE)

• Lab Findings:
• -↓ platelet count
• -↑ bleeding time
• -↑ megakaryocytes

• Treatment:
• -IVIg
• -Splenectomy (remove source of Ab and platelet destruction)

• Epidemiology:
• -usually seen in adult females

• Pathophysiology:
• -deficiency in ADAMTS13
• -usually due to acquired autoantibody
• -ADAMTS13 is a metalloprotease that degrades vWF multimers for eventual degradation
• -large vWF monomers can be cleaved, leading to abnormal platelet adhesion
• -↓ platelet survival

• Labs:
• -↓ platelet count
• -↑ bleeding time
• -schistocytes
• -↑ LDH

• Symptoms:
• -neurologic sx
• -renal sx
• -fever
• -thrombocytopenia
• -microangiopathic hemolytic anemia

• Etiology:
• -children with E coli O157:H7 dysentery (undercooked beef)

• Pathophysiology:
• -due to endothelial damage by drugs or infection
• -E coli verotoxin damages endothelial cells resulting in platelet microthrombi

• Labs:
• -↓ platelet count
• -↑ bleeding time
• -schistocytes
• -↑ LDH

• Symptoms:
• -neurologic sx (more common in TTP)
• -renal sx (more common in HUS)
• -fever
• -thrombocytopenia
• -microangiopathic hemolytic anemia

• -von Willebrand's disease
• -DIC

• Epidemiology:
• -most common inherited coagulation disorder
• -mild
• -most common is autosomal dominant

• Pathophysiology:
• -low vWF impairs platelet adhesion
• -vWF also stabilizes FVIII (can impair intrinsic pathway depending on severity)

• Presentation:
• -mild mucosal and skin bleeding

• Labs:
• -normal platelet count
• -↑ bleeding time
• -↑ or normal PTT
• -normal PT

• Diagnosis:
• -Ristocetin Cofactor Assay: induces platelet aggregation by causing vWF to bind GpIb

• Treatment:
• -desmopressin (ADH analog): causes release of vWF stored in endothelium

• Pathophysiology:
• -widespread activation of clotting leads to a deficiency in clotting factors which creates a bleeding state

• Etiology:
• -Sepsis (GN: endotoxins and cytokines induce endothelial cells to make TF)
• -Trauma
• -Obstetric Complications (tissue thromboplastin in amniotic fluid activates coagulation)
• -Pancreatitis
• -Malignancy (adenocarcinoma: mucin activates coagulation)
• -Nephrotic Syndrome
• -Transfusion

"STOP Making New Thrombi"

• Labs:
• -schistocytes
• -↑ fibrin split products (D-dimers)
• -↓ fibrinogen
• -↓ factors V and VIII
• -↓ platelet count
• -↑ bleeding time
• -↑ PT
• -↑ PTT

• Treatment:
• -address underlying cause
• -transfuse blood products

• Diseases:
• Factor V Leiden
• Prothrombin Gene Mutation
• Antithrombin Deficiency
• Protein C or S Deficiency

• Common Presentations:
• -recurrent DVTs at a young age

• Epidemiology:
• -most common inherited cause of hypercoagulable state in whites

• Pathophysiology:
• -mutated factor V that is resistant to degradation by activated protein C

• Pathophysiology:
• -mutation in 3' UTR that increases production of prothrombin → venous clots
• -increased prothrombin leads to increased thrombin and increased clots

• Pathophysiology:
• -inherited deficiency of antithrombin
• -decreases the protective effect of heparin-like molecules produced by endothelium
• -increases risk for thrombus
• -HLM activate ATIII which inactivates thrombin and coagulation factors

• Labs:
• -↑ in PTT is blunted after heparin administration

• Pathophysiology:
• -inability to inactivate factors V and VIII

• Presentation:
• -increased risk of warfarin skin necrosis (warfarin therapy causes deficiency of C and S first due to shorter half life)

• -infection transmission (low)
• -transfusion reactions
• -iron overload
• -hypocalcemia (citrate is a calcium chelator)
• -hyperkalemia (RBCs may lyse in old blood units)

• Dosage Effect:
• -↑ Hb and O2 carrying capacity

• Clinical Use:
• -acute blood loss
• -severe anemia

• Dosage Effect:
• -↑ platelet count

• Clinical Use:
• -stop significant bleeding
• -thrombocytopenia
• -qualitative platelet defects

• Dosage Effect:
• -↑ coagulation factor levels

• Clinical Use:
• -DIC
• -cirrhosis
• -warfarin OD

• Dosage Effect:
• -contains: fibrinogen, factor VIII, factor XIII, vWF, fibronectin

• Clinical Use:
• -tx coagulation factor deficiencies involve fibrinogen and factor VIII