THROMBOCYTOPENIA

Definitions

 The normal platelet count in adults ranges from 150,000 to

450,000/microL, with mean values of 237,000 and 266,000/microL in
males and females, respectively
 Thrombocytopenia is defined as a platelet count less than
150,000/microL (150 x 10(9)/L)
 Thrombocytopenia is not usually detected clinically until the platelet
count has fallen to levels significantly below 100,000/microL
 Surgical bleeding due solely to a reduction in the number of platelets
does not generally occur until the platelet count is less than
50,000/microL, and clinical or spontaneous bleeding does not occur until
the platelet count is less than 10,000 to 20,000/microL.

Overview of platelet kinetics

 Platelets are produced in the bone marrow from megakaryocytes which

are derived from more primitive precursors
 The megakaryocyte produces platelets by cytoplasmic shedding directly
into bone marrow sinusoids
 It has been estimated that about 1000 to 5000 platelets are produced by
each megakaryocyte.
 In normal individuals, platelet production is approximately 35,000 to
50,000/microL of whole blood per day; this value can be increased up to
eight-fold during times of increased demand
 Platelets survive in the circulation for 8 to 10 days, after which they are
removed from the circulation by cells of the monocyte-macrophage
system, perhaps as a result of programmed apoptosis
 In normal individuals, approximately one-third of the total platelet mass
is found in the spleen, in equilibrium with the circulating pool of platelets

Pathophysiology

 Analogous to the red blood cell system, the major mechanisms for a
reduced platelet count are decreased production and increased
destruction.
 Two additional mechanisms include dilutional or distributional
thrombocytopenia.

Decreased platelet production

 Platelet production by the bone marrow can be impaired when the

marrow is suppressed or damaged.
 In almost all disorders caused by marrow suppression or damage, white
cell and red cell production are also affected.
 After viral infections (e.g. rubella, mumps, varicella, parvovirus,
hepatitis C, and Epstein-Barr virus)
 Certain infectious agents are capable of damaging megakaryocytes
directly, such as the human immunodeficiency virus.
 Following chemotherapy or radiation therapy to sites of platelet
production (e.g. total nodal irradiation)
 In cases of congenital or acquired bone marrow aplasia or hypoplasia,
such as Fanconi anemia, acquired pure megakaryocytic aplasia, and
thrombocytopenia with absent radius (TAR) syndrome.
 Direct alcohol toxicity
 Vitamin B12 and folic acid deficiency

Increased platelet destruction

 Increased platelet destruction is seen in a number of conditions,

including:
 Idiopathic thrombocytopenic purpura (ITP) and systemic lupus
erythematosus, in which the mechanism in many cases is presumed to
be due to the presence of autoimmune anti-platelet antibodies
 Alloimmune destruction (posttransfusion, neonatal, post-
transplantation)
 Disseminated intravascular coagulation (DIC)
 Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome
(TTP-HUS)
 The antiphospholipid syndrome
 The HELLP syndrome (hemolytic anemia, elevated liver function
tests, and low platelet count) in pregnant women
 Certain drugs, most notably heparin, quinine, quinidine, and valproic
acid
  Following certain infections (e.g. infectious mononucleosis,
cytomegalovirus)
 Patients infected with HIV have a high incidence of
thrombocytopenia, which bears a similarity to ITP
 Physical destruction of platelets during cardiopulmonary bypass,
within giant cavernous hemangiomata (Kasabach-Merritt syndrome),
occasionally in large aortic aneurysms, and rarely in intravascular or
intracardiac metastatic lesions

Clinical presentation

 Patients with thrombocytopenia may be asymptomatic and

thrombocytopenia may be first detected on a routine complete blood
count.
 The symptomatic presentation of thrombocytopenia is bleeding,
characteristically mucosal and cutaneous.
 Mucosal bleeding may be manifest as epistaxis and gingival bleeding,
and large bullous hemorrhages may appear on the buccal mucosa due to
the lack of vessel protection afforded by the submucosal tissue.
 Bleeding into the skin is manifested as petechiae or superficial
ecchymoses.
 Menorrhagia (menstrual flow that does not taper after more than three
days) and metrorrhagia (uterine bleeding between periods) are also
common and there may be persistent, profuse bleeding from superficial
cuts.
 Patients with thrombocytopenia tend to bleed immediately after vascular
trauma; they do not experience the delayed bleeding that is characteristic
of patients with coagulation disorders such as hemophilia.
 Posttraumatic or postoperative surgical bleeding usually responds to local
measures, but may persist for hours or days after small injuries.
 Bleeding into the central nervous system rarely occurs; when it does
there is often preceding trauma, but it is the most common cause of death
due to thrombocytopenia.
 The pattern of bleeding in patients with thrombocytopenia (and in
patients with disordered platelet function) differs from that seen in
patients with coagulation disorders such as hemophilia, in that the latter
group has delayed bleeding that begins several hours or a day after
trauma, because normal platelet function can provide temporary
hemostasis.
 Patients with coagulation disorders also have deep bleeding (into tissues,
muscles, and joints), minimal bleeding after minor cuts, more delayed
bleeding, more postsurgical bleeding, and tend not to have petechiae

Treatment

 Zidovudine: Zidovudine (AZT) has been the mainstay of therapy of

PHAT.
 Despite its well-recognized potential for suppression of myeloid and
erythroid precursors, AZT increases platelet production in kinetic studies
of HIV-infected individuals
 There is much less information on the impact of other antiretroviral
medications or combination regimens on PHAT. A review of early
experience with didanosine monotherapy showed a small but statistically
significant increase of peripheral platelet counts within four weeks in
more than 160 HIV-positive patients.
 Mean platelet counts at baseline and four weeks were 175,000 and
197,000/microL, respectively (p<0.05)