HEMATOLOGY REVIEW-2

Arwa A Al-Qahtani MBBS, SBFM, ABFM

Consultant Family Medicine
PMAH, Riyadh, SA
30/05/2021
 Objectives
• Blood cells physiology
• RBC abnormalities
– Anemia
– Erythrocytosis
• WBC abnormalities
• Platelet abnormalities
– Thrombocytopenia
– Thrombocytosis
• PANCYTOPENIA
 WBC
• Reference ranges for differential white
blood cell count in normal adults is as
follows:
• The normal range: 4 – 11x10^9 /L
• Neutrophils - 2.0–7.0×10 9/l (40–80%)
• Lymphocytes - 1.0–3.0×10 9/l (20–40%)
• Monocytes - 0.2–1.0×10 9/l (2–10%)
• Eosinophils - 0.02–0.5×10 9/l (1–6%)
• Basophils - 0.02–0.1×10 9/l (< 1–2%)
• MEDSCAPE
• the absolute count of each of the cell
types is more useful than the total
• The total white count may be misleading;
e.g. abnormally low neutrophils with an
elevated lymphocyte count may produce a
total white count that falls within the
reference range.
• As a result the total white count should not
be considered in isolation.
The type of cell affected depends upon its primary
function:

In bacterial infections, neutrophils are most

commonly affected

In viral infections, lymphocytes are most

commonly affected

In parasitic infections, eosinophils are most

commonly affected.
• polymorphneuclear leukocytes
(PMN,s)

• Nucleus 3-5 lobes.

• Diameter 10-14 µm

• 50-70% WBC
=2.5-7.5x10^9/ L

• Function: Phagocytosis of bacteria

and cell debris

• Numbers rise with all manner of

stress, especially bacterial infections
Neutrophils
The most common cause of marked
neutrophilia is a bacterial infection.
• T cells: cellular
• (for viral infections)

• B cells: humoral
(antibody)

• Natural Killer Cells

• Lymphocytosis – may indicate
_ Viral infection
e.g. Infectious mononucleosis, CMV or pertussis.
_ Bacterial infection
e.g. TB

• Lymphopenia – caused by
_Stress.
_Steroid therapy
_ Irradiation
 Monocytes
Monocytes are cells that consume dead or
damaged cells. They are the “clean-up crew”.
 Basophils
are cells that release histamines during allergic
reactions.
 Eosinophils
are cells that kill parasites and contribute to
allergic reactions.
• (Leukocytosis) may indicate:
– Infectious diseases
– Inflammatory disease (such as rheumatoid arthritis or
allergy)
– Leukemia
– Severe emotional or physical stress
– Tissue damage (e.g. necrosis,or burns)

• (Leukopenia) may result from:

– Decreased WBC production from BM.
– Irradiation.
– Exposure to chemical or drugs.
 Q
A 50-year-old man presents with 3 days of fever, diffuse bone pain, and
extreme weakness. He denies any sick contacts.
On examination, there is conjunctival pallor, dried blood on the nasal
mucosa, and petechiae on both lower extremities. There is no
lymphadenopathy or hepatosplenomegaly.
CBC shows hemoglobin 7.9 g/dL,
leukocyte count 23,600, and
platelet count 14,000. Urinalysis and chest x-ray are normal. The
The blood smear in this patient shows an Auer rod.
What is the most likely diagnosis?

a)Multiple myeloma
b)Acute myeloid leukemia (AML)
c)Chronic myeloid leukemia(CML)
d)Acute lymphocytic leukemia (ALL)
 Q
A 50-year-old man presents with 3 days of fever, diffuse bone pain, and
extreme weakness. He denies any sick contacts.
On examination, there is conjunctival pallor, dried blood on the nasal
mucosa, and petechiae on both lower extremities. There is no
lymphadenopathy or hepatosplenomegaly.
CBC shows hemoglobin 7.9 g/dL,
leukocyte count 23,600, and
platelet count 14,000. Urinalysis and chest x-ray are normal. The
The blood smear in this patient shows an Auer rod.
What is the most likely diagnosis?

a)Multiple myeloma
b)Acute myeloid leukemia (AML)
c)Chronic myeloid leukemia(CML)
d)Acute lymphocytic leukemia (ALL)
 Explanation
• Patients with acute myeloid leukemia (AML) usually present with
nonspecific symptoms such as fever, bone pain, headache, night
sweats, and fatigue.
• Bone pain is attributed to the expansion of the marrow by leukemic
cells.
• Laboratory abnormalities include anemia and thrombocytopenia
• The blood smear in this patient shows a leukemic myeloblast
containing an Auer rod.

• Acute lymphocytic leukemia (ALL) is less common in adults, and

patients usually have generalized lymphadenopathy. Auer rods are
found in myeloblasts but not in lymphoblasts of ALL.
 Leukemia
• A type of cancer found in blood & bone
marrow

• Rapid production of abnormal WBC.

• These abnormal WBCs are not able to fight

infection and impair the ability of the bone
marrow to produce RBC & platelets.
Types of Leukemia
 Leukemia
(Rapid production of WBC)

Lymphoid stem cell Myeloid STEM CELL

-High WBC
IF HIGH - Low platelets and RBS

SEE blast cell Blast Cells

+ acute/ - chronic
+Acute/ - chronic

AML (adult)
ALL(child)
Auer body-> AmL

Philadelphia -- -CML
 Clinical tips:
• Myeloperoxidase stain means Aure rods
which is characteristic for AML.

• The 2 primary concerns with leukemia are:

– Neutropenia (↑infection)
– Thrombocytopenia (↑bleeding)

• CLL most common leukemia in adult

• ALL most common leukemia in children
• Leukemia can be presented with
leukopenia

• Anemia in leukemia caused by:

• Bone marrow infiltrate
• Hypersplensim
• Autoimmune hemolytic anemia
OTHER MALIGNANCIES
 Other malignancies
• Lymphoma
• Multiple Myloma
 LYMPHOMA
Definition
• collection of lymphoid malignancies in
which malignant lymphocytes accumulate
at lymph nodes and lymphoid tissues
• leading to lymphadenopathy, extranodal
disease, and constitutional symptoms
 APPROACH TO
LYMPHADENOPATHY
HISTORY
• constitutional/B-symptoms: seen
in TB, lymphoma, other
malignancies
• growth pattern: acute vs. chronic
• exposures: cats (cat scratch –
Bartonella henselae), ticks (Lyme
disease – Borrelia burgdorferi),
and high
• risk behaviours (HIV)
• joint pain/swelling, rashes
(connective tissue disorder)
• pruritus (seen in Hodgkin
lymphoma)
• medications (can cause serum
sickness lymphadenopathy)
 CLINICAL FEATURES
• determine if lymphadenopathy is localized or generalized
• localized: typically reactive or neoplastic
– cervical (bacterial/mycobacterial infections, ENT malignancies, and
metastatic cancer)
– supraclavicular
• right (mediastinal, bronchogenic, esophageal cancer)
• left (gastric, gall bladder, pancreas, renal, and testicular/ovarian cancer)
• axillary (cat scratch fever, breast cancer, and metastatic
cancer)
• epitrochlear (infections, sarcoidosis, and lymphoma)
• check for splenomegaly, constitutional symptoms
 INVESTIGATIONS
• CBC and differential, blood film
• if generalized, consider tuberculin test, HIV RNA, VDRL, Monospot®/EBV
serology, ANA, and imaging
• if localized and no symptoms suggestive of malignancy, can observe 3-4
wk (if no resolution biopsy)
• excisional biopsy is preferred as it preserves node architecture (essential
for diagnosing lymphoma)
• in areas difficult to access (retroperitoneal, mediastinal/hilar) multiple core
biopsies may be more practical/feasible
• FNA should NOT be used for diagnostic purposes in
lymphoproliferative disease (excisional biopsy is the gold standard)
• FNA is helpful for recurrence of solid tumour malignancy
• imaging such as U/S or CT can provide more info, but generally adds little
to diagnosis
 Multiple myloma

• Malignant proliferation of Plasma Cells

 Symptoms
• Asymptomatic in 34% of cases (present
with abnormal
labs: Anemia, Proteinuria, Hypercalcemia)
• Back pain or bone pain (58%)
• Fatigue (32%)
• Pathologic Fracture (up to 34-40% of
cases)
• Anorexia and weight loss (24%)
 Labs: Initial
• Comprehensive Metabolic Panel
(including Serum Calcium, Serum
Albumin and protein, Renal Function tests,
electrolytes)
• Complete Blood Count with
plateletsNormochromic Normocytic
Anemia
 Confirmatory test
•
Serum Protein Electrophoresis and Urine
Protein electrophoresis for Monoclonal
Peak
 Q
A 60-year-old man presents with vague left upper quadrant abdominal
fullness. He also has fatigue, malaise, and weight loss. Physical examination
reveals splenomegaly but no peripheral lymphadenopathy. CBC shows
Hb: 12 g/dL (normal 14-18)
Leukocytes: 40,000/μL (normal 4300-10,800) with increased basophils and myelocytes
but no blast forms
Platelet count: 500,000/μL (normal 150,000-400,000)
Bone marrow biopsy shows hypercellular marrow.
Cytogenic analysis shows Philadelphia chromosome .
•Which of the following is the most likely diagnosis?
a)Acute myeloid leukemia
b)Chronic myeloid leukemia
c)Chronic lymphocytic leukemia
d)Acute lymphocytic leukemia
 Q
A 60-year-old man presents with vague left upper quadrant abdominal
fullness. He also has fatigue, malaise, and weight loss. Physical examination
reveals splenomegaly but no peripheral lymphadenopathy. CBC shows
Hb: 12 g/dL (normal 14-18)
Leukocytes: 40,000/μL (normal 4300-10,800) with increased basophils and myelocytes
but no blast forms
Platelet count: 500,000/μL (normal 150,000-400,000)
Bone marrow biopsy shows hypercellular marrow.
Cytogenic analysis shows Philadelphia chromosome .
•Which of the following is the most likely diagnosis?
a)Acute myeloid leukemia
b)Chronic myeloid leukemia
c)Chronic lymphocytic leukemia
d)Acute lymphocytic leukemia
• This patient has chronic myeloid leukemia (CML).
• Patients may be asymptomatic and diagnosed by abnormal CBC
found incidentally, or patients may present with symptoms of fatigue,
malaise, weight loss, early satiety, or left upper quadrant pain due to
splenomegaly.
• Patients with CML typically have a normocytic anemia, leukocytosis
with mature cells more than immature cells, and thrombocytosis.

• Diagnosis can be confirmed with bone marrow biopsy and

cytogenetic analysis
 Case
A 63-year-old man has fatigue & frequent
nosebleeds over 4 months. He feels
abdominal fullness.
OE: afebrile, pale. Splenomegaly is
present, but the liver is not appreciably
enlarged.
 Case
• Which of the following is the most likely
diagnosis?

A.Acute myelogenous leukemia -AML

B.Anemia of chronic disease
C.Chronic myelogenous leukemia- CML
D.Multiple myeloma
E.Thrombotic thrombocytopenia purpura -TTP
 Case 2
• The correct answer is A. AML is the clonal proliferation of
blasts that are unable to differentiate into mature myeloid
cells. The median age at presentation is 65 years and this
form accounts for >80% of leukemias in adults.

• Common symptoms at presentation are those resulting from

bone marrow failure, including fatigue, dizziness, or dyspnea
on exertion. Infection is common due to low levels of mature
neutrophils, and there are often signs of organ infiltration by
blasts, usually the spleen, liver, and gums. CBC count reveals
a greatly elevated WBC count and thrombocytopenia, while
the peripheral smear shows a predominance of immature
myeloid cells, which stain positively with myeloperoxidase.
 Case
• Which of the following is the most likely
diagnosis?

A.Acute myelogenous leukemia -AML

B.Anemia of chronic disease
C.Chronic myelogenous leukemia- CML
D.Multiple myeloma
E.Thrombotic thrombocytopenia purpura -TTP
 Case 2
• Answer B is incorrect. Anemia of chronic disease is often associated with renal
failure and results from decreased erythropoietin production. Anemia develops from
the lack of stimulus driving red blood cell maturation. The peripheral smear usually is
normocytic with occasional presence of burr cells.

• Answer C is incorrect. CML also involves the myeloid lineage of cells, but in CML
they retain the ability to differentiate. As a result, peripheral smear should show an
abundance of myeloid cells in all stages of differentiation, including blasts. Most
patients present in the chronic phase of the disease. Cytology in the vast majority of
cases shows the presence of the Philadelphia chromosome.

• Answer D is incorrect. Multiple myeloma can produce anemia and recurrent

infections due to bone marrow failure. However, renal disease is much more
common, and bone pain due to increased osteoclast activity and lytic lesions is seen.

• Answer E is incorrect. Thrombotic thrombocytopenia purpura is characterized by

microangiopathic hemolytic anemia and thrombocytopenia. Peripheral smear should
show schistocytes without increased blasts.
• CLL with Autoimmune haemolytic anemia

• The presence of lymphocytosis and

splenomegaly in this age group is very
suggested of CLL

• Anemia in leukemia maybe caused by

bone marrow infiltrate, hypersplensim, or
autoimmune haemolytic anemia.
 Q
A 30-year-old woman with Graves disease has been
started on propylthiouracil. She complains of low-grade
fever, chills, and sore throat. Which of the following is the
most important initial step in evaluating this patient’s fever?
a)Serum TSH
b)CBC with differential
c)Chest x-ray
d)Blood cultures
 Q
A 30-year-old woman with Graves disease has been
started on propylthiouracil. She complains of low-grade
fever, chills, and sore throat. Which of the following is the
most important initial step in evaluating this patient’s fever?
a)Serum TSH
b)CBC with differential
c)Chest x-ray
d)Blood cultures
 Explanation
• Propylthiouracil often causes a mild
leukopenia that does not require
discontinuation of the drug.
• Drug-induced agranulocytosis, however, is
a life-threatening complication occurring in
0.1% to 0.2% of patients on antithyroid
medications and requires immediate
discontinuation
 PLATLETS
• A normal platelet count ranges from
150 – 450 × 109/L.
 HEMOSTASIS
1. VASCULAR PHASE
2. PLATELET PHASE
3. COAGULATION PHASE
4. FIBRINOLYTIC PHASE
 Lab Tests
Hemostasis •CBC-Plt
•BT,(CT)
BV Injury •PT
Tissue Factor •PTT
Neural

Blood Vessel Platelet Coagulation

Constriction Aggregation Cascade
Primary hemostatic plug

Reduced Platelet
Activation Fibrin
Blood flow formation
Plt Study
Morphology
Stable Hemostatic Plug Function
Antibody
 THE CLOTTING MECHANISM

INTRINSIC EXTRINSIC
Collagen Tissue Thromboplastin
XII
XI VII
IX
VIII

V FIBRINOGEN
(I)

PROTHROMBIN THROMBIN
(II) (III) FIBRIN
 HEMOSTASIS
DEPENDENT UPON:
! Vessel Wall Integrity
" Adequate Numbers of Platelets
# Proper Functioning Platelets
$ Adequate Levels of Clotting Factors
% Proper Function of Fibrinolytic Pathway
 LABORATORY EVALUATION
• PLATELET COUNT
• BLEEDING TIME (BT)
• PROTHROMBIN TIME (PT)
• PARTIAL THROMBOPLASTIN TIME
(PTT)
• THROMBIN TIME (TT)
 PLATELET COUNT
& NORMAL 100,000 - 400,000
CELLS/MM3

< 100,000 Thrombocytopenia

50,000 - 100,000Mild Thrombocytopenia

< 50,000 Sev Thrombocytopenia

 BLEEDING TIME

'PROVIDES ASSESSMENT OF
PLATELET COUNT AND FUNCTION

NORMAL VALUE
2-8 MINUTES
 PROTHROMBIN TIME
! Measures Effectiveness of the Extrinsic
Pathway
! Mnemonic - PET

NORMAL VALUE
10-15 SECS
 PARTIAL THROMBOPLASTIN TIME

' Measures Effectiveness of the Intrinsic

Pathway
'Mnemonic - PITT

NORMAL VALUE
25-40 SECS
 THROMBIN TIME

! Time for Thrombin To Convert

Fibrinogen Fibrin
! A Measure of Fibrinolytic Pathway

NORMAL VALUE
9-13 SECS
BLEEDING DISORDERS
 So What Causes Bleeding
Disorders?
&VESSEL DEFECTS ?
&PLATELET DISORDERS
&FACTOR DEFICIENCIES
&OTHER DISORDERS ?
 VESSEL DEFECTS

! VITAMIN C DEFICIENCY

! BACTERIAL & VIRAL INFECTIONS

! ACQUIRED &
!HEREDITARY CONDITIONS
Vascular defect - cont.
! Infectious and hypersensitivity

vasculitides
- Rickettsial and meningococcal infections
- Henoch-Schonlein purpura (immune)
 FACTOR DEFICIENCIES
(CONGENITAL)

" HEMOPHILIA A

" HEMOPHILIA B

" von
WILLEBRAND’S
DISEASE
 FACTOR DEFICIENCIES
"HEMOPHILIA A (Classic Hemophilia)
• 80-85% of all Hemophiliacs
• Deficiency of Factor VIII
• Lab Results - Prolonged PTT

!HEMOPHILIA B (Christmas Disease)

!10-15% of all Hemophiliacs
!Deficiency of Factor IX
!Lab Test - Prolonged PTT
 Hemophilia A and B

Hemophilia A Hemophilia B

Coagulation factor deficiency Factor VIII Factor IX

Inheritance X-linked X-linked

recessive recessive

Incidence 1/10,000 males 1/50,000

males

Severity Related to factor level

<1% - Severe - spontaneous bleeding
1-5% - Moderate - bleeding with mild
injury
5-25% - Mild - bleeding with surgery or
trauma

Complications Soft tissue bleeding

 Hemophilia
Clinical manifestations (hemophilia A & B are
indistinguishable)
Hemarthrosis (most common)
Fixed joints
Soft tissue hematomas (e.g., muscle)
Muscle atrophy
Shortened tendons
Other sites of bleeding
Urinary tract
CNS, neck (may be life-threatening)
Prolonged bleeding after surgery or dental
extractions
Hemarthrosis (acute)
 FACTOR DEFICIENCIES
! VON WILLEBRAND’S DISEASE
!Deficiency of VWF & amount of Factor VIII
!Lab Results - Prolonged BT, PTT
von Willebrand Disease: Clinical Features
• von Willebrand factor
– Synthesis in endothelium and megakaryocytes
– Forms large multimer
– Carrier of factor VIII
– Anchors platelets to subendothelium
– Bridge between platelets
• Inheritance - autosomal dominant
• Incidence - 1/10,000
• Clinical features - mucocutaneous bleeding
 Treatment of von Willebrand Disease

• Cryoprecipitate
– Source of fibrinogen, factor VIII and VWF
– Only plasma fraction that consistently contains VWF multimers

• DDAVP (deamino-8-arginine vasopressin)

– ­ plasma VWF levels by stimulating secretion from endothelium
– Duration of response is variable
– Not generally used in type 2 disease
– Dosage 0.3 µg/kg q 12 hr IV

• Factor VIII concentrate (Intermediate purity)

– Virally inactivated product
 Vitamin K deficiency

• Source of vitamin K Green vegetables

Synthesized by intestinal
flora

• Required for synthesis Factors II, VII, IX ,X

Protein C and S

• Causes of deficiency Malnutrition

Biliary obstruction
Malabsorption
Antibiotic therapy

• Treatment Vitamin K
Fresh frozen plasma
 PLATELET DISORDERS

! THROMBOCYTOPENIA

! THROMBOCYTOPATHY
THROMBOCYTOPENIA

INADEQUATE NUMBER
OF PLATELETS
THROMBOCYTOPATHY
ADEQUATE NUMBER BUT
ABNORMAL FUNCTION
Idiopathic thrombocytopenic
purpura
 also known as immune thrombocytopenia
• primary: isolated thrombocytopenia (platelet count <100 x 10/L) with no other
cause of
thrombocytopenia
• secondary: thrombocytopenia associated with another condition (e.g. HIV,
HCV, SLE, CLL)
• drug-induced: drug-dependent platelet antibodies causing platelet destruction
 Thrombotic
Thrombocytopenic Purpura
• TTP ( Thrombotic Thrombocytopenic Purpura)

• The combination of acute onset neurological abnormalities in

association of microangopathic hemolytic anemia,
thrombocytopenia, and renal failure is highly suggestive of TTP

Causes of TTP:
• Infection ( Ecoli, shigella, HIV).
• Connective tissue dis.SLE, scleroderma.
• malignant hypertention.
• malignancy ( adenocarcinoma).
• drugs (ticlpidine, oral contraceptive, 5FU, cyclosporin.
• post transplantation.
Thrombocytosis
Pancytopenia
 Case 1
• •A 70-year-old woman is What is most likely diagnosis?
evaluated for a 4-month history
of easy bruisability. Her
medical history is otherwise A.TTP
noncontributory. B.HUS
• Physical examination, C.DIC
including vital signs, is normal.
D.ITP
• The complete blood count
indicates a hemoglobin of 11.5
g/dL(115 g/L), leukocyte count
of 4500/μL(4.5 ×109/L), and
platelet count of 35,000/μL(35
×109/L).
 Case 1
• •A 70-year-old woman is What is most likely diagnosis?
evaluated for a 4-month history
of easy bruisability. Her
medical history is otherwise A.TTP
noncontributory. B.HUS
• Physical examination, C.DIC
including vital signs, is normal.
D.ITP
• The complete blood count
indicates a hemoglobin of 11.5
g/dL(115 g/L), leukocyte count
of 4500/μL(4.5 ×109/L), and
platelet count of 35,000/μL(35
×109/L).
 EXPLANATION
• Autoimmune disorder IgG Ab binds to
platelets.
• No splenomegaly.
• 80 % have no associated disease (
idiopathic)
• Associated with : HIV, SLE, CLL.
• Plt < 20,000 or with bleeding should
treated with corticosteroid ± IVIG
• A platelet count from 30 to 50 × 103 per μL
rarely manifests as purpura. A count from
10 to 30 × 103 per μL may cause bleeding
with minimal trauma. A platelet count less
than 5 × 103 per μL may cause
spontaneous bleeding and constitutes a
hematologic emergency
 Case 2
• A 30-year-old woman in the 34th week of pregnancy is
evaluated for nausea, vomiting, and severe right upper-
quadrant pain that has worsened over the past 3 days. The
remainder of the medical history is noncontributory.
• On examination, the temperature and blood pressure are
normal, but there is 1+ bilateral lower-extremity edema, right
upper quadrant tenderness, and several petechiae on the
dorsum of both feet.
• Laboratory studies indicate a hemoglobin of 9 g/dL, leukocyte
count of 8500/μL, and platelet count of 23,000/μL . AST120
U/L, ALT 110 U/L, total bilirubin is 1.8 mg/dL(30.78μmol/L),
and creatinine is 1.8 mg/dL(159.16μmol/L). The peripheral
blood smear shows numerous schistocytes.
• What is the most appropriate treatment for
this patient?

• What is the most likely diagnosis?

• Immediate delivery of the fetus
•
• The HELLP syndrome
 Case 4
• A 64-year-old man is evaluated in the emergency
department for a 3-day history of progressive, severe
fatigue, dyspnea, forgetfulness, an inability to
concentrate, and excessive thirst. He has also had lower
back pain for the past 3 months.

• Examination: the patient is confused. The pulse is

120/min, and the blood pressure is 110/75 mmHg. The
oral mucosa is dry, and the spine is tender to light
percussion. Laboratory studies indicate a hematocritof
27%, leukocyte count of 13,5000/μL(13.5 ×109/L) ,
platelet count of 160,000/μL(160 ×109/L), serum calcium
concentration of 14.5 mg/dL(3.37mmol/L), and serumc
reatinine concentration of 3.5 mg/dL(309.47μmol/L).
• What is the most likely diagnosis?

• What is the most appropriate investigation

to support the diagnosis?
• Multiple myeloma

• abnormal findings on laboratory testing

(about 34% of patients asymptomatic on
presentation), such as:
• anemia
• elevated erythrocyte sedimentation rate
(ESR)
• elevated serum total protein hypercalcemia
• renal insufficiency
• diagnostic confirmation usually based on
monoclonal protein (M-protein) in serum or
urine and/or lyticlesions on x-ray with
increased number of plasma cells in bone
marrow.

• Hypercalcemia, bone pain, anemia, and

clusters of large plasma cells on bone
marrow aspirate smear are diagnostic of
multiple myeloma.
 Case 5
• A 64-year-old man is evaluated in the clinic for severe fatigue
that has worsened over the past 3 months and recurrent
epistaxis.

• On physical examination, petechiae are noted in the lower

extremities.

• Laboratory studies was done :

• leukocyte count of 1200/μL (1.2 x 109/L), neutrophil count of
300/μL (0.3 × 109/L),platelet count of 15,000/μL (15 × 109/L),
and a reticulocyte count of 0.2% of erythrocytes.

• Bone marrow showed absent hematopoietic precursors.

v What are the lab abnormalities?
• Pancytopenia

v Give DDX?
• Drugs/chemicals
• Radiation
• Viral infections
• Idiopathic

v What is the most likely diagnosis?

• aplastic anemia
 Q
• A 25-year-old woman complains of persistent bleeding for 5 days
after a dental extraction. She has noticed easy bruisability since
childhood, and was given a blood transfusion at age 17 because of
prolonged bleed- ing after an apparently minor cut. She denies
ecchymoses or bleeding into joints. Her father has noticed similar
symptoms but has not sought medical care. Physical examination is
normal except for mild oozing from the den- tal site. She does not
have splenomegaly or enlarged lymph nodes. Her CBC is normal,
with a platelet count of 230,000. Her prothrombin time is nor- mal,
but the partial thromboplastin time is mildly prolonged. The bleeding
time is 12 minutes (normal 3-9 minutes). What is most appropriate
way to control her bleeding?
a) Factor VIII concentrate
b) Fresh frozen plasma
c) Desmopressin (DDAVP)
d) Whole blood transfusion
e) Single donor platelets
• 308. The answer is c. This woman’s life long history of excessive
bleeding suggests an inherited bleeding problem, as does the
positive family history. The prolonged PTT indicates a deficiency of
factors VIII, IX, XI, or XII, but the commonest of these deficiencies
(classic hemophilia A and Christmas disease, or hemophilia B) are
vanishingly rare in women. Furthermore, the continued oozing from
dental sites and the absence of ecchymoses or hemarthroses
suggest a platelet function disorder, as does the prolonged bleeding
time. Von Willebrand disease is an autosomal dominant condition
that leads to both platelet and factor VIII dysfunction and is the
likeliest