The document discusses platelet disorders, beginning with normal platelet function in hemostasis. It then covers the classification of platelet disorders as quantitative (related to platelet count) or qualitative (related to platelet function). Quantitative disorders include thrombocytopenia (low platelet count) and thrombocytosis (high platelet count). Thrombocytopenia can be caused by decreased production, increased destruction, sequestration, or loss. Qualitative disorders involve defects in adhesion, aggregation, or secretion. Specific qualitative disorders discussed include Bernard-Soulier syndrome, Glanzmann's thrombasthenia, storage pool deficiencies, and drug-induced disorders. Diagnosis involves evaluating history, symptoms, platelet count, bleeding time, and specialized tests of

1. ‫تعالى‬ ‫قال‬(َ‫م‬ْ‫ال‬َ‫و‬ ِّ‫ه‬ِّ‫د‬ْ‫م‬َ‫ح‬ِّ‫ب‬ ُ‫د‬ْ‫ع‬َّ‫الر‬ ُ‫ح‬ِّ‫ب‬َ‫س‬ُ‫ي‬‫و‬ُ‫ي‬َ‫و‬ ِّ‫ه‬ِّ‫ت‬َ‫ف‬‫ي‬ ِّ‫خ‬ ْ‫ن‬ِّ‫م‬ ُ‫َة‬‫ك‬ِّ‫ئ‬ َ‫َل‬ُ‫ل‬ِّ‫س‬ْ‫ر‬
ُ‫ه‬َ‫و‬ ُ‫ء‬‫َا‬‫ش‬َ‫ي‬ ‫ن‬َ‫م‬ ‫ا‬َ‫ه‬ِّ‫ب‬ ُ‫يب‬ ِّ‫ُص‬‫ي‬َ‫ف‬ َ‫ق‬ِّ‫ع‬‫ا‬َ‫و‬َّ‫ص‬‫ال‬َ‫و‬ُ‫ه‬َ‫و‬ ِّ َّ‫اَّلل‬ ‫ي‬ِّ‫ف‬ َ‫ون‬ُ‫ل‬ِّ‫د‬‫ا‬َ‫ج‬ُ‫ي‬ ْ‫م‬
(ِّ‫ل‬‫ا‬َ‫ح‬ِّ‫م‬ْ‫ال‬ ُ‫د‬‫ي‬ِّ‫د‬َ‫ش‬

2. By:
Romissaa Aly
Demonstrator of Oral medicine,Periodontology,
Diagnosis and Radiology
Al-Azhar Univerisity

3. Platelets are a key component in the
hemostatic system. Current nomenclature
categorizes platelet disorders based on
normal, increased, or decreased platelet
counts; normal or abnormal platelet
function; and whether the diseases are
inherited or acquired.

5. Normal Platelet Function :
The primary function of platelets is their role in
hemostasis. Briefly, under normal physiological
conditions, platelets will adhere to and begin to spread
over the surface of subendothelial cells exposed by
damage to the vascular endothelium.(1) Adhesion is
dependent on the platelet membrane glycoprotein lb
complex. The von Willebrand factor (vWF) is required
for both adhesion and spreading.

6. urokinase plasminogen activator; uPAR, urokinase plasminogen
activator
receptor.

9. The spreading phenomenon involves a platelet
shape change from discoid to spheroid, with the
extension of pseudopodia. (2) During this time,
the platelets will also begin to release the contents
of their dense and alpha granules including
adenosine diphosphate (ADP), serotonin, vWF,
and fibrinogen.

10. The combined effects of platelet shape change and
release prepare the initial layer of adherent
platelets for interaction with circulating
inactivated platelets and the start of platelet
aggregation. Aggregation, unlike adhesion,
requires fibrinogen binding to the platelet
membrane glycoprotein Ilb/IIIa complex.3
The subsequent interaction of the aggregated
platelet mass and coagulation factors leads to the
formation of a stable hemostatic plug.

11. Activated
platelets also express P-selectin on their surface, which leads to recruitment of
leukocytes via interactions between platelet P-selectin and P-selectin
glycoprotein ligand-1 (PSGL-1) expressed on the surface of leukocytes.

18. Diagnosis and Evaluation of Bleeding
Disorders: Bleeding disorders in which there are
platelet abnormalities may exist as independent
entities, in conjunction with coagulation factor
and/or vascular defects, or as secondary
manifestations of numerous other diseases.
Careful examination of the patient's history,
physical condition, and laboratory results are all
essential for proper diagnosis and management.|

19. Citation: Bleeding Disorders, Stern SC, Cifu AS, Altkorn D. Symptom to Diagnosis: An Evidence-Based Guide, 3e; 2014. Available at:
https://accessmedicine.mhmedical.com/content.aspx?bookid=1088&sectionid=61697470 Accessed: June 24, 2018
Copyright © 2018 McGraw-Hill Education. All rights reserved
Diagnostic approach to the bleeding patient.
aPTT, activated partial thromboplastin time; CAD, coronary artery disease; DIC, disseminated intravascular coagulation; GI, gastrointestinal; INR,
international normalized ratio; ITP, idiopathic thrombocytopenia purpura; NSAIDs, nonsteroidal antiinflammatory drugs; PT, prothrombin time; TTP,
thrombotic thrombocytopenic purpura.

20. History and Clinical Symptoms: patient history
about the nature and frequency of any past bleeding
episodes as well as familial information, current
medications (prescription and over-the-counter-
preparations), and information regarding any past
and/or coexisting medical conditions. The classic
clinical symptoms that suggest a platelet disorder
include hemorrhages that are superficial (as opposed
to the deep bleeding more commonly associated with
coagulation factor defects), petechial hemorrhages,
and bleedings that stop after the application of
pressure and do not spontaneously restart several
hours or days later.

21. Laboratory Evaluation :The screening tools most
readily available for the evaluation of platelet
function are the platelet count, bleeding time,
and observation of clot retraction. More rigorous
testing, such as aggregation studies, determination of
platelet factor 3 (PF 3) levels, and methods for the
detection of antiplatelet antibodies, should be carried
out when indicated by preliminary test results and/or
the patient history and clinical symptoms .(4-5)

22. The normal range for platelet counts in healthy
adults is 150 to 440xl03L. Bleeding time tests
evaluate the function of platelets and are also
influenced by the availability of vWF. When
performed properly, prolongation of the
template bleeding time in the presence of
adequate numbers of platelets indicates
defective platelet function. (8)

24. Classification
of Platelet
Disorders :
Quantitative
Platelet
Disorders
Qualititative
Platelet
Disorders

25. Thrombocytopenia is characterized primarily by
an abnormally low platelet count. This category
includes a wide variety of both congenital and
acquired platelet disorders that can be further
subdivided based on the causative
mechanism—decreased or defective
production, abnormal sequestration,
enhanced destruction, or excessive loss of
platelets. (10)

27. Decreased or Defective Production :

29. Enhanced Destruction :Thrombocytopenia
due to the enhanced destruction of platelets
occurs in a variety of circumstances. Many of
these conditions have a suspected or
confirmed underlying immune
mechanism,. Nonimmunological
mechanisms include platelet consumption
disorders and situations in which there is
direct destruction of platelets by physical
forces or toxic substances

31. Consumption Disorders: Thrombocytopenia due
to platelet consumption may occur in association
with numerous conditions, including sepsis,
neoplasms, massive hemolysis. The
predominant consumption disorder present
is disseminated intravascular coagulation
(DIC),. The initial event occurring in DIC is
activation of the coagulation mechanism with
possible formation of circulating thrombi that may
cause obstruction of the microcirculation of organs.

33. disseminated intravascular
coagulation

34. Thrombotic thrombocytopenic
purpura : (TTP) is a disorder of
unknown etiology that is characterized by
thrombocytopenia, renal failure, hemolytic
anemia, shistocytes on blood smear, and
neurological abnormalities.

35. Direct Destruction :
Thrombocytopenia due to destruction of
platelets by physical forces in extensive burns.
More commonly, direct destruction of platelets is
the result of circulating substances that act as
platelet toxins. Ristocetin, protamine
sulfate, and heparin are capable of
causing thrombocytopenia by this type of
mechanism.17-18. venom or viral toxins may
directly destroy platelets.

36. Immune-Related Mechanisms :
Antiplatelet antibodies are associated
with premature platelet destruction in
several different clinically defined
thrombocytopenias. Patients with
idiopathic (immune) thrombocytopenic
purpura (ITP).

37. Platelet antibodies commonly are produced in
patients receiving multiple platelet transfusions.
Some patients may fail to increase their platelet
count following transfusions because the transfused
platelets are destroyed by the antibodies. Such
patients are said to be "refractory" to random donor
platelet transfusions and need to have immune-
compatible platelet donors selected via HLA
compatibility testing or a platelet cross match
assay.

38. Neonatal isoimmune thrombocytopenia
occurs in newborns whose mothers produce an
antiplatelet antibody in response to a fetal
antigen inherited from the father and absent in
the mother, analogous to erythroblastosis
fetalis.20 Similarly, mothers with ITP may also
produce an antibody that may cross the
placenta and produce thrombocytopenia in the
neonate. (21)

39. Abnormal Sequestration :
Under normal physiological conditions,
approximately one third of the body's total
platelet mass is sequestered within the spleen.
A transient thrombocytopenia may be seen in
association with hypothermic conditions as
a result of increased platelet sequestration, but
this is usually clinically insignificant.
Hypersplenism can lead to an increase
sequestration of all blood cell lines, although
the resulting thrombocytopenia is rarely severe

42. Excessive Loss:
Thrombocytopenia due to the excessive loss of
platelets may occur as the result of extensive
hemorrhage or extracorporeal perfusion..(22) In both
of these situations the bone marrow is unable to
produce platelets quickly enough to compensate for the
acute reduction in the level of circulating platelets.

49. Thrombocytosis:
Thrombocytosis is generally defined as a platelet count above 400,000 per /iL..

50. Primary thrombocytosis: Examination of
peripheral blood smears show a broad range in
platelet size and shape, including giant platelets
and large aggregates. Patients with primary
thrombocytosis may experience thrombotic
and/or bleeding complications. Hemorrhagic
complications are more common and may result
from defects in platelet function, consumption of
coagulation factors, and/or the ulceration of
infarcts

51. Secondary Thrombocytosis: The most
common conditions that can result in
secondary thrombocytosis are listed in
Table III. The mechanisms that influence
the overproduction of platelets include
overcompensation for previously
decreased platelet levels, presence of a
platelet-stimulating factor in the plasma
associated with an increased sedimentation
rate anemia, iron deficiency.24

52. While secondary thrombocytosis is
generally an asymptomatic condition, some
patients may experience thrombotic
complications due to spontaneous platelet
clumping or increased platelet coagulant
activity. Unlike primary thrombocytosis,
abnormal bleeding problems are rare with
secondary thrombocytosis

53. Hemorrhagic manifestations : skin
manifestations: bruising, subcutaneous hematomas,
ecchymoses, and epistaxis or gum bleeding. Petechiae
are never seen. A history of gastrointestinal blood loss
(melena and/or hematemesis) or biological evidence in
favor of chronic occult blood loss may be evidenced at
diagnosis. Secondary bleeding, eventually life-
threatening can also occur after trauma or surgery

55. Qualitative Platelet Disorders:
Congenital and acquired
Congenital platelet defects in which there are
qualitative abnormalities classified based on
platelet function that is abnormal—adhesion,
aggregation, or secretion. The most widely used
tool for the diagnosis and/or differentiation of
these disorders is the study of platelet
aggregation patterns

57. Defects of Adhesion
Bernard-Soulier syndrome, also referred to as
the giant platelet syndrome. The mode of
inheritance of this disorder is autosomal
recessive, and the hemorrhagic manifestations
may be very severe. Bernard-Soulier
platelets have reduced levels of
membrane glycoprotein lb (GP lb), which
is involved in the binding of vWF and
adhesion.25

58. Defects of Primary Aggregation:
Glanzmann's thrombasthenia is
an autosomal recessive disorder
characterized by defective platelet
aggregation. This disorder is quite rare
and the bleeding manifestations vary
greatly among patients with seemingly
similar degrees of platelet abnormalities..

59. Defects of Secretion:
Congenital disorders in which there are
abnormalities of platelet secretion can be
divided into two groups—those in which the
platelets contain decreased levels of a
secretable substance, or storage pool
deficiencies (SPDs), and those which have defects
in the physical process of secretion itself, or
primary secretory defects. Bleeding episodes in
these patients are usually minor. Platelet
aggregation studies usually demonstrate abnormal
aggregation with collagen and an absence of a
second wavein response to ADP.

60. The SPD classification is a
heterogeneous group of disorders in
which one or more substances normally
present in platelet granules are
decreased or absent. In general,
these platelets appear to be of
normal size, but cases have been
reported where particularly small
or large platelets were noted.

61. Deficiencies of substances stored within
the dense granules (ADP, serotonin,
calcium, and/or pyrophosphate, specifically)
are more common than alpha granule
deficiencies (beta-thromboglobulin, platelet
factor 4, and/ or platelet-derived growth
factor deficiencies). 27Platelets lacking dense
granules usually appear morphologically
normal, while those with alpha granule
deficiencies have an overall gray appearance.

62. Acquired Qualitative Defects:
Idiopathic Thrombocytopeni Purpura: The
increased destruction of platelets that occurs in
idiopathic thrombocytopenia purpura (ITP) is often the
result of antiplatelet antibodies. Platelet functional
abnormalities, including aggregation defects and
reduced levels of platelet factor 3 (PF 3), have also been
reported in patients with ITP. 28 The biochemical basis
of these defects and their influence on hemorrhagic
complications have not yet been clearly established.

63. Drug-Induced Disorders:
A variety of drugs have been observed to
influence platelet function through a number of
different mechanisms. Aspirin ingestion directly
affects platelet function by irreversibly inhibiting
cyclooxygenase, a key enzyme in the production of
thromboxane A2, and laboratory tests reveal an
aggregation pattern similar to that observed with
SPDs. Penicillin, in high doses, has also been
shown to impair platelet aggregation.29 Dextran
and other plasma expanders appear to interfere
with both adhesion and PF 3 activity.

67. Giant platelet syndrome (Bernard-Soulier syndrome):
in which the platelets lack the ability to stick adequately to
injured blood vessel walls and as a result of this problem there
is abnormal bleeding.
The giant platelet syndrome usually presents in the newborn
period, infancy, or early childhood with bruises, nose bleeds
(epistaxis), and/or gum (gingival) bleeding. Later problems
can occur with anything which can induce bleeding such
as menstruation, trauma, surgery, or stomach ulcers.

69. Thank you