I.

DISORDERS OF PRIMARY HEMOSTASIS Loss of subcutaneous fat and elastic fibers

a. Vascular Disorders -incidence increases with advancing age
-Scurvy -the dark blotches:
-Senile Purpura Flattened
-Ehlers-Danlos Syndrome About 1-10mm in dm
-Marfan’s Syndrome Do not blanch w/ pressure (resolve slowly,
-Henoch-Schonlein Purpura often leaving a brown stain in the
b. Platelet Disorders skin age spots
-Quantitative: Thrombocytosis -lesions are limited mostly:
Thrombocytopenia Exterior surfaces of the forearm
-Qualitative: Gray Platelet Syndrome Back of the hands
Bernard-Soulier Syndrome Face and neck (occasionally)
Chediak-Higashi Syndrome -Lab result: normal except INCREASED capillary fragility
Wiskott-Aldrich Syndrome -no other bleeding manifestations
Glanzmann’s Syndrome
II. DISRODERS OF SECONDARY HEMOSTASIS MARFAN’S SYNDROME
-Coagulation factor deficiencies -caused by mutation in FBN 1 gene encoding fibrillin 1
-Von WIllebrand diseases (chromosome 15) w/ required for structural integrity of
-Factor V Leiden connective tissues and regulation of TGF-β signaling
-Circulating Inhibitors -autosomal dominant disorder
III. FIBRINOLYSIS SYSTEM -causing problem in the connective tissue all throughout
-Mechanisms the body
-Disorders -mutation results in increased protein called
tansforming growth factor β signaling
-Fibrillin: essential glycoprotein in the proper function
of extracellular matrix including biogenesis and
I. DISORDERS OF PRIMARY HEMOSTASIS maintenance of elastin fibers
-critical in the structural integrity of connective
SCURVY tissues and reservoir of growth factor
-insufficient dietary intake of Vit. C (ascorbic acid) -most common defect in the: skeletal and eyes
-results in: -life threatening defect: cardiovascular system
Scurvy defect/lesion
Decreased synthesis of collagen -Cardiovascular lesions: most life threatening features
-w/ weakening of capillary walls and the of this disorder
appearance of purpuric lesions -two most common lesions:
-if the cause cannot be determined: Mitral valve prolapse
Diagnosis is Purpura simplex (Simple vascular Of greater importance, dilation of the ascending
Purpura) or Vascular Fragility is made aorta
-findings: -loss of medial support results in progressive dilation of
Superficial ecchymoses the aortic valve ring and the root of the aorta, giving
Mild bleeding rise to severe aortic incompetence
Lab test results: must often normal -in addition, excessive TGF-β signaling in the adventitia
Cutaneous bleeding and bruising through intact may also contribute to aortic dilation
skin  w/ no vascular or platelet -thickening of the media predisposes to an _________
dysfunction detected tear, which may initiate an intramural _____ that
-involves mostly women w/ emotional problems cleaves the layers of the media called aortic dissection
-bruising is accompanied by nausea, vomiting or fever -skeletal abnormalities are the most striking
-evudence for a psychosomatic origin is equivocal characteristics of Marfan syndrome
-lab test results are invariably normal -typically, the patient is unusually tall with long
extremities fingers and toes
SENILE PURPURA -have flexible joints and scoliosis
-occurs in elderly men due to:
Lack of collagen support for small blood vessels
HENOCH-SCHONLEIN PURPURA
-AKA allergic purpura or anaphylactoid purpura
-applied to a group of nonthrombocytopenic purpuras
characterized:
Allergic manifestations, including skin rash and
edema
-allergic purpura has been associated with certain
foods and drugsm cold, insect bites and vaccinations
-term Henoch-Schonlein purpura is accompanied by:
Transient arthralgia
Nephritis
Abdominal pain
Purpuric skin lesions
 w/c are frequently confused w/ the
hemorrhagic rash of immune
Thrombocytopenic purpura
-cause:
-Autoimmune vascular injury but the pathophysiology
of the disorder is unclear
-preliminary evidence indicates that the vasculitis is
mediated by immune complexes containing IgA
abs
-allergic purpura may represent autoimmunity to
components of vessel walls
-primarily a disease of childer
Most commonly bet. 3-7 years of age
Relatively uncommon among individuals
younger than 2 and older than 20
-twice as many boys as girls are affected
-onset of disease is sudden, often following an upper
respiratory tract infection
-the infectious organism may damage the endothelial
lining of blood vessels, which results in vasculitis
-β-hemolytic streptococcus implicated infectious agent
-presenting symptoms:
Malaise, headache, fever and rash
Delayed appearance of the skin rash
 often poses difficult problem in differential
diagnosis
-skin lesions are urticarial and gradually become pinkish,
then red and finally hemorrhagic
-appearance of the lesions may be:
very rapid with itching
-lesions are described as: palpable purpura in contrast
to the perfectly flat lesions of thrombocytopenia and
most other forms of vascular purpura
Most commoly found on the feet, elbows,
knees, buttocks and chest
Brownish-red eruption is seen
Petechiae may also be present
-progress manifestations:
-development of abdominal pain, polyarthralgia,
Headaches and renal disease may develop
-renal lesions are present in 60% of patients during
the second week of the disorder
-proteinuria and hematuria are commonly present
-lab results:
-platelet ct is normal
-tests of hemostasis bleeding time and tests of
blood coagulation is normal with allergic
purpura pxts
-anemia is not present unless with severe
hemorrhagic manifestations
-WBC ct and Erythrocyte sedimentation rate is
elevated
-average duration in pediatric age group
-initial episodes is about 4 weeks
-relapses are frequent, usually after a period of
apparent well being
-prognosis is good except for patients in whom
Chronic renal dse develops
-occasionally, death from renal failure
-management is directed primarily at symptomatic
relief because there is no effective
-corticosteroids sometimes have been helpful in
alleviating symptoms
-patients recover without treatment
THROMBOCYTOSIS
-platelet count: more than 450 000/uL
-reactive thrombocytosis: to describe an elevation in
the platelet ct secondary to inflammation trauma or
other underlying and seemingly unrelated conditions
-platelet count is elevated for a limited period
- does not exceed 800 000/uL, although platelet
cts greater than 1 million/uL are occasionally
seen
-a marked and persistent elevation in the platelet count
is a hallmark of myeloproliferative disorders such as:
Polycythemia vera
Chronic myelogenous leukemia
Myelofibrosis with myeloid metaplasia (or
primary myelofibrosis)
-these conditions , platelet count often exceeds 1
million/uL
-terms thrombocythemia and thrombocytosis are often
used interchangeably
-Thrombocythemia: used only as part of description of
the myeloproliferative disorder known as essential
thrombocythemia
-in essential thrombocythemia, platelet cts typically
exceed 1 million/uL and may reach levels of several
million
-processes resulting in thrombocytosis:
Conditions assoc w/ reactive thrombocytosis
-blood loss and surgery
-splenectomy
-iron deficiency anemia
-inflammation and disease
-stress or exercise
Myeloproliferative disorders assoc w/
Thrombocytosis
-polycythemia vera
-chronic myelogenous leukemia
-myelofibrosis w/ myeloid metaplasia
-thrombocythemia: essential or primary
REACTIVE (SECONDARY) THROMBOCYTOSIS
1. reactive thrombocytosis assoc w/ hemorrhage or
surgery
2. postsplenectomy thrombocytosis
3. thrombocytosis assoc w/ iron deficiency anemia
4. thrombocytosis assoc w/ iron def anemia
5. thrombocytosis assoc w/ inflammation and disease
6. exercise induced thrombocytosis
7. rebound thrombocytosis
-platelet ct between 450 000/L and 800 000/L with no
change in platelet function can result from
Acute blood loss
Splenectomy
Childbirth
Tissue necrosis secondary to:
surgery
Chronic inflammatory dse
Infection
Exercise
Iron def. anemia
Renal disorders
Malignancy
-occasionally, pxts manifest a platelet ct of 1-2
million/uL
-in reactive thrombocytosis: platelet production
remains responsive to normal regulatory stimuli (ex.
thrombopoietin)
-morphologically normal platelets are produced
at moderately increased rate
-essential thrombocytosis: characterized by unregulated
or autonomous platelet production and platelets of
variable size
-bone marrow examination: normal to increased no. of
megakaryocytes that are normal in morphology
-platelet function test, including:
-aggregation induced various agents
-bleeding time
-both normal in reactive
thrombocytosis
-normal in pxts w/ elevated platelet ct
accompanying myeloproliferative
disorders
-reactive thrombocytosis is not associated w/:
-thrombosis, hemorrhage, or abnormal
thrombopoietin levels
-seldom produces symptoms per se and
disappears when the underlying disorder is
brought under control
REACTIVE THROMBOCYTOSIS ASSOC W/
HEMORRHAGE OR SURGERY
-Platelet ct may be low for 2-6 days (unless platelets
have been transfused)
-typically rebounds to elevated levels for several
days before returning to the prehemorrhage
level
-platelet ct typically returns to normal 10-16 days after
the episode of blood loss (major surgical procedure)
POSTSPLENECTOMY THROMBOCYTOSIS
-platelet ct can reach or exceed 1 million/L regardless of
the reason for splenectomy
-the spleen normally sequesters about one third of the
circulating platelet mass
-expect an initial increase in platelet ct 30%-50%
-the platelet ct reaches a maximum 1-3 weeks after
spelenectomy and remains elevated for 1-3 months
-in some pxts who undergo splenectomy for treatment
of chronic anemia, the count can remain elevated for
several years
THROMBOCYTOSIS ASSOCIATED W/ IRON DEFICIENCY
ANEMIA
-mild IDA secondary to chronic blood loss is associated
w/ thrombocytosis in about 50% cases
-thrombocytosis can be seen I severe IDA, but
thrombocytopenia also has been reported
-in some cases, of iron deficiency , platelet ct may be 2
million/uL
-afte iron therapy is started, the platelet ct usually
returns to normal within 7-10 days
THROMBOCYTOSIS ASSOCIATED W/ INFLAMMATION
AND DISEASE
-similar to elevations in C-reactive protein, fibrinogen,
VWF and other acute phase reactants, thrombocytosis
may be an indication of inflammation
-thrombocytosis may be found in association w/
rheumatoid arthritis, rheumatic fever, osteomyelitis,
ulcerative colitis, acute infections and malignancy
-in rheumatoid arthritis: the presence of
thrombocytosis can be correlated w/ activation of the
inflammatory process
-Kawasaki dse or syndrome causes inflammation of the
walls of small and medium sized arteries all throughout
the body
-aka mucocutaeous lymph node syndrome
because it affects lymph nodes, skin, and
mucous membranes in the mouth, nose and
throat
-acute febrile illness of infants and young
children
-boys are more likely than girls to develop the
dse
-children of of Japanese and Korean descent
have higher rates of Kawasaki dse
-self-limited acute vasculitic syndrome of
unknown origin
-acute febrile stage: lasts 2 weeks or longer, w/
fever of 40 C ̊ or higher and is unresponsive to
antibiotic therapy
-the longer the fever continues, the higher risk
of cardiovascular complications
-WBC ct can be moderately to markedly
elevated w/ left shift , and many pxts develop a
mild normochromic, normocytic anemia
-during this phase, cardiovascular complications
and aneurysms develop
-the higher the platelet ct, the higher the risk of
cardiovascular complication
-diagnosis is primarily by excluding other
disease that cause similar signs and symptoms
(ex. scarlet fever, juvenile rheumatoid arthritis ,
Stevens Johnson syndrome and toxic shock
syndrome)
-the treatment for Kawasaki dse is
administration of antiplatelet agents and
immunoglobulin
-an elevated platelet ct also may be early evidence of a
tumor (ex. Hodgkin dse) ad various carcinomas. Finally,
hemophilic pxts often have platelet ct above normal
limits, even in the absence bleeding
EXERCISE-INDUCED THROMBOCYTOSIS
-strenous exercise is a well-known cause of relative
thrombocytosis and is likely due to:
-the release of platelets from the splenic pool or
hemoconcentration by transfer of plasma water
to the extravascular compartment or both
-Normally, the platelet ct returns to its pre exercise
baseline level 30 mins after completion of exercise
REBOUND THROMBOCYTOSIS
-thrombocytosis often follows the thrombocytopenia
caused by marrow-suppressive therapy or other
condtions
-Rebound thrombocytosis usually reaches a peak 10-17
days after withdrawal of the offending drug (alcohol or
methotrexate) or after institution of therapy for the
underlying condition with w/c thrombocytopenia is
associated (vit b12 def.)
THROMBOCYTOSIS ASSOC W/ MYELOPROLIFERATIVE
-primary or autonomous thrombocytosis is a typical
finding in four chronic myeloproliferative disorders:
-polycythemia vera
-chronic myelogenous leukemia
-myelofibrosis w/ myeloid metaplasia (primary
myelofibrosis)
-essential thrombocythemia
-depending on the duration and stage of the
myeloproliferative disorder at the time of diagnosis,
may be difficult to differentiate among these disorders
ESSENTIAL THROMBOCYTHEMIA (PRIMARY)
-clonal disorder related to other chronic
myeloproliferative diseases
-most common cause of primary thrombocytosis
-characterzied by:
-peripheral blood platelet ct exceeding
1million/uL
-uncontrolled proliferation of marrow
megakaryocytes
-persistent marked elevation of the platelet count is an
absolute requirement for the diagnosis of essential
thrombocythemia
-the clinical manifestations are:
-hemorrhage
-platelet dysfunction
-thrombosis
-bleeding times are usually normal
-no specific clinical sign, symptom, or lab test that
establishes the diagnosis of essential thrombocythemia
-diagnosis must be made by ruling out the other
myeloproliferative disorders and systemic illnesses that
produce reactive thrombocytosis
-thrombosis in the microvasculature is relatively
common
-incidence at the time of diagnosis is 10-20%
-this thrombosis can lead to:
-digital pain
-digital gangrene
-erythromelalgia (throbbing, aching, and
burning sensation in the extremities (soles and
palms)
-erythromelalgia symptoms can be explained by
arteriolar inflammation and occlusive thrombosis
mediated by platelets and can be relieved for several
days by single dose of aspirin
-venous thrombosis may involve the large veins of the
legs and pelvis, hepatic veins or splenic veins
-the platelets of some patients who have experienced
thrombotic episodes:
have been shown to have increased binding
affinity for fibrinogen and to generate more
than the usual quantities of thromboxane B2
-patients have elevated levels of thromboxane B2 and
β-thromboglobulin in the blood
-findings suggest enhanced in vivo platelet activation
-explanation for the thrombotic tendencies of
patients w/ essential thrombocythemia
-primary cause of death: thrombosis
-hemorrhagic episodes < thrombotic episode in patients
w/ ET
-hemorrhagic manifestation of essential
thrombocythemia:
-mucocutaneous in nature
-w/ gastrointestinal tract bleeding- most
frequently
-other sites:
Mucous membranes of the nose and mouth
Urinary tract
Skin
-symptoms may be aggravated by aspirin use
-in an occasional pxt w/ essential thrombocythemia:
-paradoxical combination of thromboembolic
(clotting) and hemorrhagic episodes in
association w/ this condition
-pxt w/ thrombotic event may have a hemorrhagic
event later