1. What you need to know about CBC and coagulation profileBy
Prof Ahmed Abdelwarith

2. Slide credits to many contributors Including PPT & Text Books

3. Introduction

4. Hematology
Study of normal and pathologic aspects of different blood components
1-complete blood count (CBC) reports
2- Bone Marrow
3- coagulation and hemeostasis

5. Blood &Plasma
Suspension of cells in a solute of water, proteins, and electrolytes
Average volume is 5 liters
70mL per kg body weight

6. Blood &Plasma
Plasma
Blood from which the cellular components (RBCs, WBCs, platelets) have been removed by centrifuge
Color is yellow
Contains coagulation proteins (clotting factors)

7. Hematopoiesis
Development of blood cells and other formed elements
Sites vary throughout development
Fetal: yolk sac, liver, spleen
Pediatric: axial and appendicular skeleton
Adult: axial skeleton (sternum and pelvis)

8. Hematopoiesis Stem cells
Primitive; self-replicate and differentiate to become increasingly specialized progenitor cells which form mature cells
Process regulated by growth factors (interleukins, erythropoietin, thrombopoietin, G-CSF)
Early lineage division between progenitors for lymphoid and myeloid cells

9. B lymphocyte development markers
CELL ARREST X
CLONAL EXPANSION

11. Complete Blood Count White blood cells (WBC)
Differential
Neutrophils, lymphocytes, monocytes, eosinophils, basophils, bands
Must specify whether to include with CBC order
Red blood cells (RBC, HGB, HCT)
Platelets
Mean corpuscular volume (MCV)
Red cell distribution width (RDW)

12. Fish bone diagram

13. Hemoglobin & Hematocrit
Hematocrit : (packed cell volume)
It is ratio of the volume of red cell to the volume of whole blood.
M: 40.7 to 50.3 %
F: 36.1 to 44.3 %

14. Red Blood Cells
Transport oxygen via hemoglobin from lungs to peripheral tissues and organs
Normal lifespan = 120 days
Electron microscope of RBC – Biconcave disc

15. Red Blood Cells
Peripheral blood smear
Normal

16. Anemia Almost 1/3 of the world population is anemic!
Condition resulting from decrease in total body erythrocyte mass
Defined by measurement of hemoglobin concentration
Normal range
Males g/dL
Females g/dL
Almost 1/3 of the world population is anemic!
Increase in hgb that occurs in men is mostly related to effect of androgens on release of erythropoietin ; gender disparity becomes less significant in advanced age
HGB x 3 = Rough HCT

17. Manifestations related to duration and severity of anemia
Body has physiologic responses to chronic anemia such that many patients are asymptomatic until hgb < 8 g/dL

18. Anemia Symptoms Signs Easy fatigue Headache Dyspnea on exertion Pallor
Tachycardia
Systolic ejection murmur
Orthostatic hypotension

19. Anemia Decrease production -No raw material
-Malfunction of the factory
Increase destruction
Hemolysis
Sequestration
Blood loss
Acute , chronic
External , internal

20. Determining reticulocyte count and MCV are first steps in determining etiology

21. Reticulocytes 1- Reticulocyte Count Immature red blood cells
Measurement assists in determining cause of anemia
Normal = 1-2%
Must correct for degree of anemia
Observed retic count (Actual HCT/Normal HCT) = Corrected retic count

22. Reticulocyte Count
Low suggests decreased production (i.e. nutritional or bone marrow problem)
High suggests bleeding or premature destruction of red blood cells (i.e. hemolysis)

23. 2- Check the MCV

24. MCV&MCHC MCV = mean corpuscular volume HCT/RBC count= 80-100fL
small = microcytic
normal = normocytic
large = macrocytic
MCHC= mean corpuscular hemoglobin concentration HB/RBC count= 26-34%
decreased = hypochromic
normal = normochromic

25. Microcytic Anemia Microcytosis – small cells (MCV <80)
Most common type of anemia encountered in primary care
Differential diagnosis
Hemoglobinopathy (inherited)
Iron deficiency
Chronic disease (may also be normocytic)
Inflammation
Lead poisoning
Check iron studies for clarification
Be familiar with interpretation (see next slide)

26. Microcytic Anemia Microcytosis – small cells (MCV <80)
Most common type of anemia encountered in primary care
Differential diagnosis
Hemoglobinopathy (inherited)
Iron deficiency
Chronic disease (may also be normocytic)
Inflammation
Lead poisoning
Check iron studies for clarification

27. Microcytic Anemia
Peripheral blood smear
Microcytosis, Hypochromic

28. RDW ( RBCs distribution width)= 6–8 umDx
RDW
MCV
Iron deficiency  
FOLATE &VIT B12 
RECENT Hge
NORMAL .
High RDW
-Iron Deficiency Anemia: usually presents with high RDW with low MCV
-Folate and vitamin B12 deficiency anemia: usually presents with high RDW and high MCV
-Recent Hemorrhage: typical presentation is high RDW with normal MCV

29. Macrocytic Anemia Fasting homocysteine, and methylmalonic acid (MMA)
Macrocytosis – large cells (MCV >100)
Differential diagnosis
B12 deficiency
Pernicious anemia
Folate deficiency
Myelodysplasia (pre-leukemia)
Medication effect
Check vitamin B12, RBC folate,
Fasting homocysteine, and methylmalonic acid (MMA)
are elevated in subclinical B12 and folate deficiency
Medications associated with elevated MCV include…

30. Hemolytic Anemia History and physical findings Lab findings
Review PMH, FH, and medications
Jaundice
Abdominal discomfort
Lab findings
Elevated reticulocyte count
Reflects bone marrow compensating for peripheral RBC destruction
Elevated LDH
Elevated total bilirubin (indirect/unconjugated)
Decreased haptoglobin
Abnormal cells on peripheral blood smear examination

31. Hemolytic Anemia Membrane defects Enzyme defects Congenital
Hereditary spherocytosis
Splenectomy is curative
Hereditary elliptocytosis
Enzyme defects
G6PD deficiency
Affects 10% of world population
Common in patients of African descent
Precipitated by stress, infection, drugs, and fava beans
Hemolysis mostly extravascular but may be intravascular if severe case

32. Hemolytic Anemia
Acquired
Classified according to site of RBC destruction and whether mediated by immune system
Intravascular
Extravascular
Autoimmune
Non-immune
Many causes… be aware of these –
Transfusion of incompatible blood (details later)
Warm (IgG-mediated) ; most common
Cold (IgM-mediated)
Prosthetic valves
TTP/HUS
DIC
Cancer
Drugs

33. Hemolytic Anemia Coomb’s Test (DAT)
Used to screen for autoimmune hemolytic anemia

34. Polycythemia / Erythrocytosis
Abnormal elevation of hemoglobin
Rule out “relative” polcythemia caused by contraction of plasma volume, e.g. dehydration
Primary
Polycythemia Vera
Secondary
RBC production in response to increased EPO production
EPO level is usually high

35. White Blood Cells Differential Neutrophils 45-65% Lymphocytes 15-40%
“Segs” / “Polys”
Lymphocytes %
Monocytes 2-8%
Eosinophils 0-5%
Basophils 0-3%
Do you remember the physiologic role of each type of WBC?

36. Leukopenia Neutropenia is most common cause Many causes
Absolute neutrophil count (ANC) < 1.5 x 109 cells/L
Many causes
Viral infections
Epstein-Barr, Hepatitis B, HIV
Drugs *
Careful review of medications ;
Splenomegaly
Autoimmune disorders = SLE (lupus), Rheumatoid
Bone marrow disorders

37. Neutropenia Common Medicinal Causes of Neutropenia Cytotoxic agents
Antibiotics (Penicillins, Cephalosporins, Sulfonamides)
Anticonvulsants
NSAIDs
Antithyroid agents (Methimazole, PTU)
Phenothiazines
Allopurinol
Cimetidine
Diuretics (HCTZ, Spironolactone)

38. Leukocytosis WBC count > 11,000
Determine which type of WBC is leading to the leukocytosis
Neutrophilia = most common
Infection
Connective tissue disorders
Medications (especially steroids, growth factors)
Cancer (CML and solid tumors)
Myeloproliferative disorders
Cigarette smoking
Stress (physiologic)
Pain, seizure, trauma
Idiopathic

39. Leukocytosis
Patients with acute bacterial infection often present with neutrophilia and band formation ; i.e. “left shift”
Bands = young neutrophils
Viral infections are usually associated with low WBCs ; leukocytosis may suggest complications
Ex: bacterial pneumonia with underlying influenza infection

40. Chronic Leukemia Chronic myelogenous leukemia (CML)
Translocation between long arms of chromosomes 9 and 22 ; “Philadelphia Chromosome” ; bcr/abl protein
Patients usually middle-age at diagnosis, average age 55 years
Fatigue, fever, night sweats, abdominal fullness (splenomegaly)
Symptoms of leukostasis may be present if WBC > 500,000
Blurred vision, respiratory distress, priapism
Three phases of disease
Early / Chronic phase
Accelerated
Blast crisis

41. Chronic Leukemia CML, Vs leukomoid reaction
Can you recognize early CML from infection?
WBC usually < 50,000 with infection
WBC average 150,000 at time of diagnosis with CML
LAP score is decreased with CML
Splenomegaly NOT present with infection
Chromosomal abnormality and detection of bcr/abl protein by peripheral blood PCR is diagnostic of CML

42. Acute Leukemia
Myeloblast

43. Bleeding Disorders
Coagulation cascade

44. Bleeding Disorders
Review coagulation cascade ; general understanding is essential for clinical practice
Prothrombin time (PT) evaluates extrinsic system
Factors I, II, V, X, VII
Activated partial thromboplastin time (PTT) evaluates intrinsic system
Factors I, II, V, X, VIII, IX, XI, XII
Bleeding time reflects platelet number and function
Factor I is also called fibrinogen

45. Bleeding Disorders General approach Prolonged PT only
Warfarin (Coumadin®) therapy
Factor VII deficiency
Fibrinogen abnormality
Prolonged PTT only
Heparin therapy
Factor VIII deficiency
Congenital
Hemophilia A (X-linked)
1:5000 male births
Male and female carriers ; no racial predilection
Acquired
Factor IX deficiency – Hemophilia B / Christmas disease
Lupus anticoagulant *
Antiphospholipid antibodies *
Prolonged PT and PTT
Usually reflective of general medical condition such as DIC, vitamin K deficiency, or liver disease
Disorders of common pathway (rare)
* See page Schmaier p. 82

46. Bleeding Disorders Approach to patient
History of trauma? Time between injury and bleeding?
Ask about bleeding at times of life events
Circumcision
Tooth eruption
Dental extraction
Ear piercing
Childbirth
Menstrual cycles
Family history
Did you know 30% of patients with hemophilia have unremarkable family history?
Spontaneous mutation of X chromosome

47. Primary hemostasis – platelet and vascular function
Bleeding Disorders
Patterns of bleeding
Primary hemostasis – platelet and vascular function
Secondary hemostasis – clotting factors
CNS bleeding is leading cause of death among hemophilia patients

48. Bleeding Disorders Characteristic Primary hemostasis
Secondary hemostasis
Onset
Spontaneous and immediate
Delayed after trauma
Usual site
Skin, mucous membranes
Deep tissues / hemarthrosis
Other sites
Rare
Retroperitoneum, CNS
Examples
Thrombocytopenia, platelet defects (vWD)
Factor deficiency or inhibitor
CNS bleeding is leading cause of death among hemophilia patients

49. Bleeding Disorders
Acute hemarthrosis

50. Bleeding Disorders
Petechiae in patient with acute ITP ; platelet count = 10,000

51. Heparin-Induced Thrombocytopenia (HIT)
Occurs in 3% of patients exposed to UFH ; 0.6% with LMWH
Drop in platelet count ≥ 50% within 5-10 days of heparin exposure
May occur within 48 hours of exposure in those previously exposed to drugs
Thrombosis (NOT bleeding) is of great clinical concern
Thrombotic events detected in about half of HIT patients
Must STOP heparin and consult hematology
Direct thrombin inhibitor (alternative anticoagulant) may be started
Argatroban®
Refludan®