Thrombocytopenia

April 16, 2001, Dr. D.

Lee

What we will cover today:

Normal platelet production and survival
Thrombocytopenic bleeding
Approach to thrombocytopenia
ITP
DIC
Cases
1

Thrombocytopoiesis
PLURIPOTENT
MIXED
STEM CELL PROGENITOR
CELL

COMMITTED
PROGENITOR
CELL

RECOGNIZABLE
BONE MARROW
PRECURSOR CELL

BFU-E/CFU-E

CFU-Eos

red cell
neutrophil
monocyte
eosinophil

CFU-Baso

basophil

CFU-GM

myeloid
progenitor
cell
pluripotent
stem cell
lymphoid

pronormoblast
myeloblast
monoblast

MATURE
BLOOD
CELL

CFU-Meg

megakaryocyte

platelet

pre-T

lymphoblast

T-cell

pre-B

lymphoblast

B-cell
& plasma cell

Platelet formation

megakaryocyte

formation of
demarcation
membranes

platelets
(pro)platelets

Platelets in the circulation:

Influx, efflux, and redistribution
(+) thrombopoietin

PRODUCTION

platelet count

CIRCULATING
PLATELETS
70%

DESTRUCTION
or REMOVAL

SPLEEN
30%

Thrombopoietin
normal platelet count

thrombocytopenia

[TPO] total

normal

normal

[TPO] free

normal

increased

plasma
TPO
platelet

Thrombocytopenic bleeding
Risk of bleeding
platelet count
cause of thrombocytopenia
comorbid disease
drugs

Clinical manifestations

petechiae
purpura, ecchymoses
mucosal bleeding
menorrhagia
intracranial bleeding

40
% days with gross
hemorrhage

Risk of thrombocytopenic
hemorrhage in AML

30
20
10
0
0

20

40

60

80

100

Platelet count (x 10^9/L)

Approach to thrombocytopenia
THROMBOCYTOPENIA
rule out pseudothrombocytopenia
SEQUESTRATION

PRODUCTION

look for splenomegaly

bone marrow investigation

review meds

Causes of splenomegaly
infection
inflammation
congestion
maligancy
red cell disorders
storage diseases

DESTRUCTION
look for underlying disorders
review meds

aplasia
immune
infiltration
auto-immune (ITP, SLE
ineffective megakaryopoiesis
drugs
eg. MDS
infections
selective impairment of platelet allo-immune
non-immune
production
sepsis
DIC, TTP, HUS
hypertensive disorders of pregnancy

ITP
idiopathic autoimmune platelet
destruction
#1 cause of isolated thrombocytopenia in
otherwise healthy young persons
a diagnosis of exclusion

ITP: Clinical features

occurs in any age or sex, but typically
young female
can be preceeded by viral infection
signs and symptoms depend on platelet
count
onset usually insidious

ITP: Laboratory features

ITP IS A DIAGNOSIS OF EXCLUSION

no sensitive and specific test for ITP
isolated thrombocytopenia
increased MPV
normal PT, PTT
bone marrow investigation not essential in
straightforward cases

10

ITP: Treatment
Patient is not bleeding
plt > 50: Rx not indicated
plt 20-50: Rx usually not needed, monitor
closely
plt < 20: Rx indicated with one or more of:

prednisone
IVIG
anti-D if Rh pos
splenectomy if relapsing severe ITP

(No role for prophylactic platelet transfusion, even if plt = 0)

11

ITP: Treatment
Patient is bleeding
For serious bleeding (eg. CNS,
retroperitoneal, GI)

Prednisone and IVIG

Transfuse platelets
consider urgent splenectomy
Provide other supportive/resuscitative care as needed

12

ITP: Prognosis
Children: usually permanent remission
Adults: usually relapsing (chronic ITP), but
course is relatively benign.

13

Disseminated Intravascular
Coagulation (DIC)
DIC is characterized by
the systemic activation of the coagulation system
followed by activation of fibrinolytic system
high thrombin and plasmin generation

DIC is not a disease itself, but is a

manifestation of a serious underlying
disorder.

14

Causes of DIC
Infection

- bacterial sepsis, viral

infections

Neoplasm
- AML, adenocarcinoma
Obstetrical disorders
- retained dead fetus,
abruption, etc

Trauma/surgery
Others

- brain injury, crush, burns, etc.

- acute hemolytic transfusion

reaction, etc.

15

Pathophysiology of DIC
PATHOPHYSIOLOGIC
EVENTS

LABORATORY
MANIFESTATIONS

CLINICAL
MANIFESTATIONS

underlying disorder

tissue factor release

activation of intrinsic
pathway of coagulation
(systemic thrombin
generation)

depletion of clotting factors

prolonged PT, PTT
thromboctyopenia (consumption)
hemorrhage
depletion of physiologic anticoagulants
decreased fibrinogen

generalized intravascular
fibrin deposition

activation of
fibrinolytic system
(systemic plasmin
generation)

microangiopathic hemolytic anemia

thrombosis/infarction
increased FDP and D-dimer

16

Treatment of DIC
treat the underlying disease
replacement therapy

cryoprecipitate
FFP
platelet concentrate
packed red cells

consider additional pharmacologic therapy

controversial or investigational agents
AT, APC, PC concentrate, heparin, antifibrinolytic
agents.

17

The most important stuff to

remember:
Approach to thrombocytopenia
ITP diagnosis and management
When to worry about a low platelet count

18

Thrombocytopenia: Case 1
A previously healthy 23 year old female competitive lacrosse
player presents to your office with a three day history of increased
bruising and petechiae. Her only medications are naproxen and an
oral contraceptive. Physical exam shows petchiae on the legs and
several small bruises on the extensor surfaces.
Leukocytes (x 109/L)
Hemoglobin (g/L)
MCV (fL)
Platelet count (x 109/L)
MPV (fL)

6.8
130
87
11
12.5

[4.0 - 11.0]
[120-160]
[80 - 100]
[150 - 450]
[7.4 -10.4]
19

Thrombocytopenia: Case 1
How do you approach this problem diagnostically?

How you manage this patient and what do you advise her
about her activities and medications?

20

Thrombocytopenia: Case 2
A CBC comes back on a 75 year old man who is new to your practice.
Leukocytes (x 109/L)
Hemoglobin (g/L)
MCV (fL)
Platelet count (x 109/L)
MPV (fL)
Reticulocytes (x 109/L)

3.6
127
101.5
56
8.1
86

[4.0 - 11.0]
[140 - 180]
[80 - 100]
[150 - 450]
[7.4 -10.4]
[18 - 94]

Neutrophils (x 109/L)
Lymphocytes (x 109/L)
Monocytes (x 109/L)
Eosinophils (x 109/L)
Basophils (x 109/L)

1.3
1.6
0.7
0
0

[2-7.5.0]
[1.5-4.0]
[0.2-0.8]
[0-0.7]
[0-0.1]

No platelet clumps are seen on the peripheral blood film.

21

Thrombocytopenia: Case 2
What is the differential diagnosis?
B12, folate deficiency
hypersplenism
alcohol
medications
myelodysplasia
other bone marrow pathology
How do you sort this out?
Obtain a history and examine the patient.
Ultrasound of the abdomen (spleen size).
Serum B12, RBC folate
bone marrow investigation.

22

Thrombocytopenia
What we hopefully have covered today:
Normal platelet production and survival
Thrombocytopenic bleeding
Approach to thrombocytopenia
ITP
DIC
Cases
23