T = THALASSEMIA
A = ANEMIA OF CHRONIC DISEASE (microcytic or normocytic; iron use by the body is impaired) - chronic inflammatory states such as malignancy, infection and rheumatologic diseases
I = IRON DEFICIENCY - Blood loss (GI, GU, vaginal, trauma), iron-deficient diet, celiac disease, atrophic gastritis, renal failure on EPO, pulmonary hemosiderosis, intravascular hemolysis
***History: FATIGUE, WEAKNESS, BRITTLE NAILS, and PICA.
***PE: GLOSSITIS, ANGULAR CHEILITIS, and KOILONYCHIA ("Spoon Nails")
***TODDLERS, ADOLESCENT GIRLS, and WOMEN OF CHILDBEARING AGE are most commonly affected.
***Iron deficiency anemia in an ELDERLY PATIENT may be due to COLORECTAL CANCER and must therefore be evaluated to RULE OUT MALIGNANCY
***SEQUENCE OF IRON DEFICIENCY:
↓ iron → ↑ TIBC → ↓ Hb → ↓ MCV → Hypochromia
***Peripheral blood smear shows MICROCYTIC, HYPOCHROMIC RBC's ("DOUGHNUT CELLS") with enlarged areas of CENTRAL PALLOR and a LOW RETICULOCYTE COUNT.
***LOW SERUM FERRITIN reflects LOW BODY STORES of iron and CONFIRMS THE DIAGNOSIS. However, ferritin is also an ACUTE-PHASE REACTANT and may thus obscure evidence of iron deficiency.
***RED CELL DISTRIBUTION WIDTH (RDW) elevation is a HIGHLY SPECIFIC TEST FOR IRON DEFICIENCY
***Treat with REPLACEMENT IRON FOR 4-6 MONTHS. Oral iron sulfate may lead to NAUSEA, CONSTIPATION, DIARRHEA, and ABDOMINAL PAIN. ANTACIDS may INTERFERE with IRON ABSORPTION.
L = LEAD POISONING
S = SIDEROBLASTIC
- The anticoagulant effect of warfarin is mediated by inhibition of the vitamin K-dependent gamma-carboxylation of coagulation factors II, VII, IX, and X\
- The full anticoagulant effect of warfarin is DELAYED until the normal clotting factors are cleared from the circulation, and the PEAK EFFECT does NOT occur until 36 to 72 hours AFTER drug administration
- During the first few days of warfarin therapy, PROLONGATION of the PT mainly reflects DEPRESSION of FACTOR VII, which has a half-life of only five to seven hours; thus, the INTRINSIC coagulation pathway that does not require factor VII REMAINS INTACT. Equilibrium levels of factors II, IX, and X are not reached until about one week after the initiation of therapy.
***Using warfarin, the therapeutic range for the INR varies with the clinical indication. For MOST indications the recommended range is 2.0 to 3.0
***INR may not be directly applicable to patients with liver disease
Prolongation of the aPTT can occur with a DEFICIENCY of, or an inhibitor to, ANY of the clotting factors EXCEPT for FACTOR VII
PROLONGED aPTT; NORMAL PT
- Deficiency of factors VIII, IX, or XI
- Deficiency of factor XII, prekallikrein, or HMW kininogen
- von Willebrand disease (variable)
- Heparin administration
- Inhibitor of factors VIII, IX, XI, or XII
- Acquired von Willebrand disease
- Lupus anticoagulant
PROLONGED aPTT; PROLONGED PT
- Deficiency of prothrombin, fibrinogen, or factors V or X
- Combined factor deficiencies
- Liver disease
- Disseminated intravascular coagulation
- Supratherapeutic doses of anticoagulants
- Severe vitamin K deficiency
- Combined heparin and warfarin administration
- Argatroban with or without warfarin administration
- Inhibitor of prothrombin, fibrinogen, or factors V or X
- Primary amyloidosis-associated factor X deficiency
If the aPTT is PROLONGED and the PT (INR) is NORMAL, the problem is localized to the INTRINSIC pathway.
***The most common INHERITED bleeding disorders giving this picture are von Willebrand disease and isolated deficiencies of factors VIII, IX, and XI, while common ACQUIRED causes of this pattern are heparin therapy and the lupus anticoagulant phenomenon caused by the presence of antiphospholipid antibodies
If the aPTT is NORMAL and the PT (INR) is PROLONGED, the problem lies in the extrinsic pathway (factor VII)
***The most common acquired causes are the use of warfarin, chronic liver disease, and vitamin K deficiency
If both the aPTT and PT (INR) are prolonged, the problem is likely to be in the FINAL COMMON PATHWAY.
***In this situation, the thrombin time (TT) can be used to assess the last step in the pathway, conversion of fibrinogen to fibrin. If the TT is NORMAL, the problem resides in the common pathway, due to abnormalities in factors II (prothrombin), V, or X. Common acquired conditions giving a prolonged PT and aPTT and a normal TT are liver disease, disseminated intravascular coagulation, and overanticoagulation with warfarin.
If BOTH the aPTT and the PT (INR) are normal in a patient with a bleeding diathesis, then thrombocytopenia, mild deficiency of von Willebrand factor, platelet dysfunction, vascular disorders, and, rarely, factor XIII deficiency or a disorder of the fibrinolytic system should be considered.
After an ABNORMALITY in a clotting test has been detected, it is important to differentiate between a clotting factor deficiency and an inhibitor (eg, an antibody or other interfering substance (eg, heparin) directed against the clotting factor). This is accomplished by performing a MIXING STUDY, in which the patient's plasma is mixed in a 1:1 ratio with normal pooled plasma, and the abnormal tests are repeated.
***As a general rule, clotting tests will give NORMAL values when 50 percent activity of the involved coagulation factors are present. Thus, if the clotting test returns to NORMAL after a 1:1 dilution with normal pooled plasma, a FACTOR DEFICIENCY was the cause of the abnormal test.
***Most agents that INHIBIT clotting factor activity (such as antibodies) will not be effectively diluted out after addition of an equal volume of normal pooled plasma. Thus, if the test remains ABNORMAL after 1:1 dilution, an INHIBITOR was the cause of the abnormal test.
***Some inhibitors may give NORMAL results when tested IMMEDIATELY after 1:1 dilution; incubation of the diluted sample for up to two hours at 37ºC may resolve this issue. As an example, delayed reactivity is characteristic of factor VIII inhibitors
(1) Platelet defects (qualitative or quantitative)
* Mucocutaneous bleeding (oral cavity, nasal, gastrointestinal, and genitourinary sites)
* Excessive bleeding after minor cuts - Yes
* Petechiae - Common
* Ecchymoses - Generally small and superficial; may be significant, depending upon the defect or degree of thrombocytopenia
* Hemarthroses, muscle hematomas - Uncommon
* Bleeding with invasive procedures, including surgery - Often immediate, with degree of bleeding dependent upon the severity of the defect, ranging from none (eg, mild degrees of thrombocytopenia or mild platelet function defect) to mild to severe (eg, Glanzmann thrombasthenia)
(2) Clotting factor deficiencies (eg, factor VIII or factor IX deficiencies)
* Deep tissue bleeding (including joints and muscles)
* Excessive bleeding after minor cuts - Not usually
* Petechiae - Uncommon
* Ecchymoses - May develop large subcutaneous and soft tissue hematomas
* Hemarthroses, muscle hematomas - Common in severe deficiency states or in association with injury in those with mild to moderate deficiency states
* Bleeding with invasive procedures, including surgery - May be associated either with procedural bleeding or delayed bleeding, depending upon the type and severity of the defect
(1) Formation of the platelet plug ─ Platelets are activated at the site of vascular injury to form a platelet plug that provides the initial hemostatic response, including exposure of procoagulant phospholipids on the platelet surface and the assembly of components of the clotting cascade.
(2) Clot formation ─ Generation or exposure of tissue factor at the wound site, its interaction with factor VII and the subsequent generation of activated factor X, are the primary physiologic events in initiating clotting, while components of the intrinsic pathway (ie, factors VIII, IX, XI) are responsible for amplification of this process.
(3) Termination of clotting ─ The termination phase of coagulation involves antithrombin, tissue factor pathway inhibitor and the protein C pathway. This phase is critical in mediating the extent of clot formation, as demonstrated by the thrombotic disorders present in individuals with abnormalities in this pathway.
(4) Clot lysis ─ To restore vessel patency, the clot must be organized and removed. Plasminogen binds fibrin and tissue plasminogen activator (tPA) leading to active, proteolytic plasmin, which cleaves fibrin, fibrinogen, and a variety of plasma proteins and clotting factors. The plasminogen/plasminogen-activator system is complex, paralleling the coagulation cascade