Anemia and Coagulation - Dr. Barrons

What is polycythemia?

Too many RBCs

Too much Hgb and Hct

What is anemia?

Too few RBCs

Too little Hgb and Hct

What is normal range of RBCs for males and females?

Males: 4.5 - 5.9 x 106 cells/mL

Females: 4.1 - 5.1 x106 cells/mL

What is an immature RBC called?

Reticulocyte (

What is Reticulocytosis?

Increased production of immature RBCs

What is the normal range of Hgb for males and females?

Males: 14 - 17.5 g/dL;

Females: 12.3 - 15.3 g/dL

What is Hgb count a direct indication of?

Direct indication of the oxygen-transport capacity of blood

What is Hgb count most used to assess in practice? (loss of what)

Most used to assess acute RBC loss and RBC needs

What is the normal range of Hct in males and females?

Males: 42-50%

Females: 36- 45%

What is Hct a measure of?

Percentage of volume of blood that is composed of erythrocytes

- Also known as the packed cell volume

What are the usual threshold lab values for anemia?

Anemia = 4 -> 12 -> 36 (RBC-> Hgb -> Hct)= thresholds for anemia

What lab value is the gold standard for identifying and monitoring anemia?

Hgb

What is RBC indices and what is it's purpose?

RBC indices = appearance of the RBC

-Classifies the anemia

-Helps identify Cause: nutritional vs. non-nutritional

•Mean Corpuscular Volume (MCV): ----

•Mean Corpuscular Hemoglobin (MCH): ------

•Red blood cell distribution & width (RDW): ---- -------

•Reticulocyte count: -------- --- --------

•Mean Corpuscular Volume (MCV): Size

•Mean Corpuscular Hemoglobin (MCH): Color

•Red blood cell distribution & width (RDW): Size variation

•Reticulocyte count: Immature RBC content

What is the normal range for MCV?

Normal range = 80- 96 fL/cell

What is considered a high MCV?

High MCV (> 96) = "macrocytic"

-RBCs are larger than normal

-Causes= Vitamin B12 or Folate deficiency

What is considered a low MCV?

Low MCV (< 80) = "microcytic"

-RBCs are smaller than normal

-Causes = Iron deficiency

What is the normal range of MCH? What does MCH estimate?

Normal range = 27- 33 pg/cell

Estimates amount of hemoglobin per RBC

What is a high MCH?

High MCH (> 33) :

-Causes= Vitamin B12 or Folate deficiency (hyperchromic)

What is a low MCH?

Low MCH (< 27)

-Causes = Iron deficiency = hypochromic (pale)

What is the normal range of RDW?

Normal range= 11.5 - 14.5%

What does a high RDW indicate?

High RDW indicates variation in RBC size= "anisocytosis"

Seen in Iron deficiency or macrocytic anemias

-Early indicator of deficiencies

What does a low RDW indicate?

No clinical relevance of low RDW

What is a normal range of reticulocytes?

0.5 to 2.5% of total RBCs

Reticulocyte count reflect bone marrow productivity

(T/F)

True

What causes increased reticulocyte count?

Acute RBC destruction or loss

What caused decreased reticulocyte count?

Bone marrow suppression

What is the typical presentation of anemia?

Hgb 10-12:

Hgb 7-10:

Hgb

Hgb 10-12: Fatigue/ Somnolence and Decreased concentration

Hgb 7-10: ↑Weakness, Fatigue & Shortness of breath

Hgb

Anemia is not a disease but a manifestation of disease

(T/F)

True, NEED to find CAUSE of anemia (to treat and ID disease)

When is anemia considered Macrocytic?

MCV >96

What typically caused macrocytic anemia?

Folate deficiency

Vit. B12 deficiency

What causes folate deficiency? What type of foods are folate rich?

Causes: Diet deficiency, Pregnancy, Autoimmune ("Celiac disease")

Found in leafy green vegetables & broccoli

What causes B12 deficiency? What type of foods are B12 rich?

Causes: Dietary deficiency (e.g.., alcoholism); Intrinsic factor deficiency ( i.e., autoimmune, bariatric surgery)

Found in meats, eggs, & diary products

Dietary cobalamin requires "------- ------"

Intrinsic Factor

When is anemia considered microcytic?

MCV

What typically caused microcytic anemia?

Iron deficiency

Erythropoeisis requires how much iron daily?

25mg Iron daily

What is serum ferritin?

Storage form of iron / small amount in serum

-↓↓Serum Ferritin in Iron deficiency anemia

-HOWEVER: Limitation = acute phase reactant

• falsely elevated in infections, fever, inflammatory reactions

What is serum iron?

Measures iron bound to transferrin

-↓'ed in Iron deficiency anemia

-↑'ed in hemolytic anemia

-HOWEVER: Large diurnal variation = use with TIBC

What is total iron binding capacity (TIBC)?

Measures iron binding capacity of transferrin

-↑↑TIBC in iron deficiency anemia (less iron/ more binding sites)

What is transferrin saturation of iron (TSAT)?

Measures = Serum iron/ TIBC X 100

-↓↓ TSAT in Iron deficiency anemia

How will each of the iron indices measure in iron deficiency anemia?

Ferritin =

TIBC =

Serum Iron =

TSAT =

Reticulocyte =

Ferritin = LOW

TIBC = HIGH

Serum Iron = LOW

TSAT = LOW

Reticulocyte = NORMAL

What is the MCV values for normocytic anemia?

80-96

What can cause normocytic anemia?

Blood loss, Hemolysis, or Chronic disease

Why can acute blood loss lead to normocytic anemia? (3)

-May have acute and/or dramatic drop in RBC, HgB, Hct

•e.g. Trauma, GI ulcers, Colon disorders (Ulcerative colitis)

-Find reticulocytosis (Bone marrow response)

•i.e., Reticulocytes > 2.5% (of total RBCs)

-Significant = decrease in Hgb > 3g/dL from baseline

•1 unit (400-500mL) of packed RBC raises Hgb by 1g/dL

What are the two causes of normocytic hemolytic anemia?

Non-Immunologic

•Hereditary: G6PD deficiency , Sickle Cell disease

Immunologic

•May be due to meds (ie., antibiotics), infections, RA, Lupus

• All have (+) Coombs test (detects antibodies surface of RBC)

What type of drop can be expected in values due to anemia of chronic disease (mild, mod, severe)?

Mild to moderate drop in RBC, HgB, Hct (slow to develop)

-Chronic infections, inflammatory diseases, neoplasms

Are all cases of anemia of chronic disease normocytic?

No, normocytic in 60- 70% of cases (remainder are microcytic)

What will anemia due to chronic inflammatory disease look like lab value wise?

DUE to Chronic Inflammatory Disease:

-Result #1: Bone marrow unable to utilize Iron stores = Ferritin is Normal

-Result #2: Increased iron stores = Lower the TIBC

What will anemia due to chronic inflammatory disease look like lab value wise?

Reticulocyte =

Ferritin =

Serum Iron =

TIBC =

TSAT =

Reticulocyte = NORMAL

Ferritin = NORMAL

Serum Iron = LOW

TIBC = LOW

TSAT = LOW

In normocytic anemia:

Reticulocyte count

Reticulocyte count

SLIDE 28 IS GOOD BREAKDOWN OF VALUES AND DISEASE STATES

SLIDE 28 IS GOOD BREAKDOWN OF VALUES AND DISEASE STATES

What is the normal range of platelets?

Normal range: 150,000 - 450,000 cells/mL

(predominantly in circulation (66%) & spleen (33%)

Platelets are the last to adhere to vascular injury

(T/F)

False, first to adhere to vascular injury

-Form weak hemostatic plug= hemostasis

Platelet adhesion stimulates clotting cascade

(T/F)

True, it allows more stable fibrin-based hemostatic plug

What is thrombocytosis?

Platelet count > 450,000 cells/ μL

What is thrombocytosis caused by?

Causes include stress, infection, trauma, malignancy

•Acute phase reactants (> 25% rise due to stressors)

What is thrombocythemia?

Thrombocythemia = platelet count > 800,000 cells/ μL

-Risk of clotting (i.e., ischemic stroke) and bleeding (i.e., GI)

What is thrombocytopenia?

Platelet count < 150,000 cells/ μL

What causes thrombocytopenia?

Hyperdestructive:

•Drugs (e.g., heparin)

•Autoimmune disease (e.g., Systemic Lupus

Erythematosus)

Hypoproductive:

•Aplastic anemia (Bone marrow failure)

Platelet count < ------ = Risk of bleeding from trauma

Platelet count < ------ = Risk of spontaneous bleeding (i.e bruising, petechiae)

Platelet count < 50,000 = Risk of bleeding from trauma

Platelet count < 20,000 = Risk of spontaneous bleeding (i.e bruising, petechiae)

What is the normal range for mean platelet volume (MPV)?

Normal range 7 - 11 fL (varies with laboratory)

Is this right?

Normal or High MPV = good production of platelets

Low MPV = impaired platelet production

Yes

-Normal or High MPV = good production of platelets

-Low MPV = impaired platelet production

Hypoproductive or Hyperdestructive?

-Thrombocytopenia + normal or High MPV=

-Thrombocytopenia + Low MPV=

-Thrombocytopenia + normal or High MPV= hyperdestructive

-Thrombocytopenia + Low MPV= hypoproductive

Why are coagulation studies useful?

Identify deficiencies in coagulation proteins

Monitor effects of anticoagulation therapy

What is the normal range and therapeutic range for INR?

•Normal range: 0.9- 1.1 (no anticoagulants or liver dysfunction)

•Therapeutic range: 2.0 - 3.0* (effect of warfarin for treatment of clotting events or clotting disorders)

4 important things to remember about INR

-INR is most used in monitoring warfarin therapy

-Not used in monitoring Direct Oral anticoagulants= DOACs

-INR of 2- 3 is therapeutic for most indications

-INR also serves as a prognostic marker in patients with advanced liver disease

What does Anti-Factor Xa (AXA) Assay measure?

§Measures plasma heparin levels

§ Uses patient plasma with and add KNOWN amount of antithrombin III and Factor Xa

§ Heparin combines with antithrombin III to inhibit factor Xa

§ Assay measures remaining levels of factor Xa (unbound/ residual)**

§ Unbound residual factor Xa as inversely proportional to the heparin concentration

What is the normal and therapeutic range for AXA?

•Normal range: < 0.5 Units/ mL

•Therapeutic range:

--0.5 to 1.0 Units/mL LMW Heparin

--0.3 to 0.7 Units/mL UF Heparin

When is the AXA test used?

AXA assay is the preferred test for monitoring heparin levels and heparin effects

What is important to consider for a patient on DOAC therapy regarding AXA testing?

DOACS often increase Anti-XA levels = interfere with heparin monitoring

--IF patient receiving DOACs and AXA level > 0.5 U/mL = use aPTT to monitor heparin

What does Activated Partial Thromboplastin time (aPTT) measure?

Measures time for patient's blood to clot (intrinsic clotting cascade + common pathways)

Identifies deficiencies in intrinsic clotting cascade (factor VIII, IX, XI, XII) & common pathway

Uses endogenous thromboplastin + other sources (i.e., kaolin) to stimulate the clotting cascade

(thromboplastin comprises only some ('partial') of the stimulation

What is normal and therapeutic range for aPPT?

•Normal range: 22- 38 sec

•Therapeutic range: 60 - 90 sec (~ 1.5 to 3 X baseline)

(Dependent on indication)

When is aPPT monitoring used?

Limited to use in Heparin monitoring in patients receiving a DOAC

Reason: DOACs may interfere with traditional anti-Xa monitoring of heparin effects

However, not all patients receiving DOAC experience this effect

Only use aPTT monitoring if anti-Xa level are elevated (>0.5 U/mL) prior to starting heparin (in patient on DOAC)

(T/F)

True

What does a D-Dimer test measure?

Byproduct of plasmin digestion of cross-linked fibrin

-D-Dimer is a fibrin degradation product

What is the normal range for D-Dimer test?

When is a D-Dimer test used?

Helps diagnose or rule out thromboembolic event

-e.g., Deep vein thrombosis (DVT)/ pulmonary embolism

-Sensitive but nonspecific marker

When is D-Dimer falsely elevated?

Malignancy, Infection, Pregnancy, & Acute Inflammation