CLINICAL FINDINGS – I3 Test 1

BIOCHEMISTRY

Folic acid/folate deficiency Nutritional deficiency

Absorption defect

- Glutamate carboxypeptidase II (GCPII) deficiency/mutation

- PCFT mutation (protein-coupled folate transporter)

- GI disease

- Reduced folate carrier deficiency

Metabolism defect

- Dihydrofolate reductase deficiency/mutation

- Serine hydroxymethyltransferase deficiency/mutation

- Methylene tetrahydrofolate reductase (MTHFR) deficiency/mutation

Methyl-folate trap

- Methionine synthase deficiency/mutation

- Vitamin B12 deficiency (See Vitamin B12 deficiency)

Hemochromatosis/iron

overload

Hepcidin deficiency

- Mutation in hepcidin gene itself (hereditary hemochromatosis)

- Mutation in regulators of hepcidin synthesis

- Liver disease

Thalassemia

Iron deficiency Nutritional deficiency (esp in rapidly growing children)

Absorption defect

- Reduced production of acid in gastric compartments

- Vitamin C deficiency

- Intestinal disorder/surgical removal (eg. Chrohn’s, celiac, etc.)

- Other molecules interacting (eg. phytanic acids in plants)

- Transporter deficiency

Bleeding (loss of ability to recycle)

- Heavy menstruation, childbirth

- Chronic, slow internal bleeding (gastrointestinal, genitourinary, pulmonary)

- Frequent blood donations

Hepheastin deficiency

- Mutation in gene

- Copper deficiency

Bacterial infection (overexpress hepcidin)

Pregnancy and lactation

Vitamin B12 deficiency Nutritional deficiency (vegans)

Absorption defect

- Parietal cells defect (no IF release)

- Autoimmunity against IF or parietal cells

- Defective TCII

- Pancreatic disease (no R factor digestion) – eg. Zollinger-Ellison syndrome

- Drug-induced (esp. those that affect gastric acid production)

Blind loop syndrome (bacteria binds to cobalamin)

ANEMIAS

Decreased RBC Stem cell defect

- Aplastic anemia

- Pure red cell anemia

- Anemia associated with myelodysplasia

- Renal failure (EPO deficiency)

Defect in cell differentiation

- DNA synthesis problem

> Folate deficiency

> Vitamin B12 deficiency

- Hb synthesis problem

> Iron deficiency

> Thalassemia

> Sideroblastic anemia (no heme)

Anemia of chronic disease

Myelophthistic anemia

Hemolytic anemia G6PD deficiency

Pyruvate kinase deficiency

Hereditary spherocytosis

Infection

Immune-mediated (IgG or IgM)

Mechanical stress

- Tight aortic stenosis

- DIC

- TTP

- Malignant hypertension

- Hemangiomas

Sickle cell anemia

Increased RBC Immune mediated

- Transfusion reaction

- Hemolytic disease of newborns

- Autoimmune hemolytic anemia

- Lymphoma

- Mycoplasma infection

Non-immune mediated

- DIC

- Burns/trauma

- Infectious disease (eg. malaria)

- Hypersplenism

Microcytic anemia Iron deficiency (See Iron deficiency)

Lead poisoning

Thalassemia

Sideroblastic anemia

Anemia of chronic disease/inflammation (slight)

Sickle cell anemia

Macrocytosis Megaloblastic anemia

Alcohol

Liver disease

Myelodysplasia

Aplastic anemia

Raised retic count

Cytotoxic drugs

Pregnancy

Megaloblastic anemia Folic acid/folate deficiency, especially:

- Methionine synthase deficiency/mutation

- Vitamin B12 deficiency (See Vitamin B12 deficiency)

Antineoplastic drugs (methotrexate, AZT)

Hereditary disorders of DNA synthesis

- Orotic aciduria

- Lesch-Nyhand syndrome

Acquired disorders of DNA synthesis

- Erythroleukemia

- Refractory sideroblastic anemia

Myelophthisic anemia Fibrosis

Bone marrow tumor

Granuloma

Normocytic anemia Aplastic anemia

Anemia of chronic disease

Myelophistic anemia

Hemolytic anemia

Acute bleeding

X-linked sideroblastic

anemia (XLSA)

δ-ALA synthase 2 deficiency/mutation

Vitamin B6 deficiency

CLOTTING

Coagulation tests

Normal PT and PTT

- Thrombocytopenia

- Qualitative platelet defect

- von Willebrand’s disease

- Factor 8 deficiency

- Vascular purpura

Isolated prolonged PT

Isolated prolonged PTT

Prolonged PT and PTT

- Final pathway factor deficiency (X, V, prothrombin, fibrinogen)

- Severe vitamin K deficiency

- DIC (disseminated intravascular coagulation)

Prolonged bleeding time

Arachidonic acid pathway defect/thromboxane defect

Hemophilia A/B

Factor 8 inhibitor

Liver disease

Platelet function disorders

- Membrane defect

- Storage pool disease

- Granule deficiency

- Diminished response to agonists

Thrombocytopenia

Severe Vitamin K deficiency

Von Willebrand’s disease

Thrombocytopenia Decrease in number/production

- Inherited

Tar baby syndrome

Wiscott-Aldrich syndrome

May-Hegglin anomaly

Alport syndrome

Acquired amegakaryoctic thrombocytopenic purpuria (AATP)

- Acquired

Radiation exposure

Drugs

Chemicals (especially benzenes)

Infections

Bone marrow dysfunction

Liver/kidney disease

Increased destruction

- Drug induced

- ITP (immune thrombocytopenic purpura)

- TTP (thrombotic thrombocytopenia purpura)

- DIC (disseminated intravascular coagulation)

- hypersplenism

Pregnancy related

- Preeclampsia

- HELLP syndrome

- Neonatal autoimmune thrombocytopenia

- Antiphospholipid Ig syndrome

Transfusion reaction

Vitamin K deficiency Antibiotics

Biliary tract disease

Fat malabsorption

Severe malnutrition

Vitamin K epoxide reductase deficiency

Vitamin K antagonist-drugs (warfarin)