1. ________ - Largest among the three, around 1 cm; also known as Bruise 2. _______ - Small pin point that measures around 1mm in diameter 3. _______ - Around 3mm 4. _____________ 5. _______ – nose bleeding 6. ___________ 7. _______ – prolonged and heavy menstruation 8. _______ – presence of blood in the urine

- CLINICAL MANIFESTATION OF PLATELET AND VASCULAR DISORDERS - Ecchymoses - Petechiae - Purpura - Mucosal Bleeding - Epistaxis - Gingival Bleeding - Menorrhagia - Hematuria

Disorders of Primary Hemostasis (Platelet Disorders) Flashcards by Queenie Mae

Disorders of Primary Hemostasis (Platelet Disorders)

QUANTITATIVE
QUALITATIVE

How well did you know this?

Not at all

Perfectly

the number of platelets

QUANTITATIVE

How well did you know this?

Not at all

Perfectly

morphology and function of the platelets

QUALITATIVE

How well did you know this?

Not at all

Perfectly

QUANTITATIVE PLATELET DISORDERS

PATHOPHYSIOLOGIC PROCESS THAT RESULTS IN THROMBOCYTOPENIA
CLINICAL MANIFESTATION OF PLATELET AND
VASCULAR DISORDERS

How well did you know this?

Not at all

Perfectly

I. Decreased Platelet Production/Impaired Platelet Production
• Two categories:
1. _____________ – incomplete development of an organ or tissue.
2. _____________ – ineffective production of the platelets
II. Increased Platelet Destruction
III. Abnormal Platelet Distribution/Pooling

PATHOPHYSIOLOGIC PROCESS THAT RESULTS IN THROMBOCYTOPENIA
Megakaryocyte Hypoplasia
Ineffective Thrombopoiesis

How well did you know this?

Not at all

Perfectly

________ - Largest among the three, around 1 cm; also known as Bruise
_______ - Small pin point that measures around 1mm in diameter
_______ - Around 3mm
_____________
_______ – nose bleeding
___________
_______ – prolonged and heavy menstruation
_______ – presence of blood in the urine

CLINICAL MANIFESTATION OF PLATELET AND
VASCULAR DISORDERS
Ecchymoses
Petechiae
Purpura
Mucosal Bleeding
Epistaxis
Gingival Bleeding
Menorrhagia
Hematuria

How well did you know this?

Not at all

Perfectly

INHERITED/CONGENITAL THROMBOCYTOPENIA

MYH9-RELATED THROMBOCYTOPENIA SYNDROMES
THROMBOCYTOPENIA WITH ABSENT RADIUS (TAR)
CONGENITAL AMEGAKARYOCYTIC
THROMBOCYTIOENIA (CAMT)
AUTOSOMAL DOMINANT THROMBOCYTOPENIA
X-LINKED THROMBOCYTOPENIA

How well did you know this?

Not at all

Perfectly

• Autosomal Dominant Thrombocytopenia
• Caused by ___________
- __________ – encodes for the non-muscle
myosin, which are the cytoskeleton of protein in
platelets.
• These include May-Hegglin anomaly, Sebastian syndrome and its variant, Epstein syndrome and Fechtner syndrome.
- Hallmark of these 4 conditions is ______________.
• Affected patients have triad of:
1. Thrombocytopenia
2. Macrothrombocytes
3. Dohle body-like inclusions in the leukocytes except with Epstein syndrome which lacks the inclusion
• Mild to moderate ___________
• PBS revealed enlarged platelets with __________

MYH9-RELATED THROMBOCYTOPENIA SYNDROMES
mutations in MYH9 gene
MYH9 Gene
Macrothrombocytopenia
thrombocytopenia
frequent giant platelets

How well did you know this?

Not at all

Perfectly

• Autosomal Recessive Thrombocytopenia
• Associated with the ______________________ (Chromosome 1)
- RBM8A – RNA binding motif protein 8a
- Responsible for coding
• _____________, first identified in 1959
- Extreme hypoplasia
• Platelet count is, approximately __________
- Hypomegakaryocytic
• ____________ are normal and marrow cellularity is normal or increased.
• __________ are low in number, absent or appear immature
• In addition to bony abnormalities, patients tend to have cardiac lesions and a high incidence of transient leukemoid reactions with elevated white blood cell (WBC) counts (sometimes with counts above 100,000/mL) in 90% of patients.
• Commonly seen among _____ and _______.
• Can be managed by _________

THROMBOCYTOPENIA WITH ABSENT RADIUS (TAR)
mutation in the RBM8A – CH 1
Rare disease
10-30 X 10^3/uL
Serum TPO levels
Megakaryocytes
infants and children
platelet transfusion

How well did you know this?

Not at all

Perfectly

• Autosomal Recessive Thrombocytopenia
• _________ in the MPL gene (Chromosome 1) – loss of TPO receptor.
- Results to reduced megakaryocyte progenitors.
• Presence of _________________, __________________ in the bone marrow.
• Family history is negative, both parents having normal platelet counts and function.
• Markedly elevated ________________.
• Patients develop progressive marrow aplasia.
• Curative therapy: _____________

CONGENITAL AMEGAKARYOCYTIC THROMBOCYTIOENIA (CAMT)
Mutation
severe thrombocytopenia
absence of megakaryocytes
serum thrombopoietin
Bone marrow transplant

How well did you know this?

Not at all

Perfectly

More severe type of thrombocytopenia with
constantly low platelet count and an early
onset of pancytopenia.

Group CAMT I

How well did you know this?

Not at all

Perfectly

Transient increased in platelet counts during
the first year of life and a later or no
development of pancytopenia.

Group CAMT II

How well did you know this?

Not at all

Perfectly

dec in rbcs, wbcs, plts

Pancytopenia

How well did you know this?

Not at all

Perfectly

• Mutation on ________ (Chromosome 10) incomplete megakaryocyte differentiation.
- Mutations in this gene appear to lead to _________________________ and the resultant thrombocytopenia.
• Mild thrombocytopenia characterized by a normal platelet survival and normal number of bone megakaryocytes (life span of plt is _______)
• Thrombocytopenia (counts ___________________) or a history of increased bruisability is apparent on early life.
• PBS shows ____________
• Abnormal platelet aggregation, normal platelet membrane glycoproteins

AUTOSOMAL DOMINANT THROMBOCYTOPENIA
ANKRD26
incomplete megakaryocyte differentiation
normal 9-12 days
20,000 to 100000/uL
platelet macrocytosis

How well did you know this?

Not at all

Perfectly

X-LINKED THROMBOCYTOPENIA

WISKOTT-ALDRICH SYNDROME (WAS)
NEONATAL THROMBOCYTOPENIA

How well did you know this?

Not at all

Perfectly

• Originally described in 1937, is now known as ________________ (carrier is the mother and passed down to son) associated with combined immunodeficiency thrombocytopenia, small platelets, eczema and an increased risk to autoimmune disorders and cancer.
• Mutations in the ________
• _________________ is the most consistent feature of WASP-associated disease.
• Ineffective thrombocytopoiesis and incomplete platelets equestration
• IgM ________, IgA and IgE _________
• WA-TER = ____________, ____________________,
__________, ______________
• Therapeutic management:
____________, _______________

WISKOTT-ALDRICH SYNDROME (WAS)
X-linked hereditary disorder
GATA1 gene
Microthrombocytopenia
decreased and increased
WiskottAldrich, Thrombocytopenia, Eczema, Recurrent infection
splenectomy, platelet transfusion

How well did you know this?

Not at all

Perfectly

• Platelet count _______________
• Thrombocytopenia may be severe platelet count of ___________
• Causes: Infection with __________, ____________,
______________, ___________
• CMV – MOST COMMON infectious agent
- CMV __________________ and their _____________, which results in impaired platelet
production. Increased platelet consumption/sequestration is another mechanism of neonatal thrombocytopenia.

NEONATAL THROMBOCYTOPENIA
less than 150,000 /ul
70,000 /ul
toxoplasma, rubella, cytomegalovirus, herpes
inhibits megakaryocytes and their precursors

How well did you know this?

Not at all

Perfectly

will reveal marked decreased or absence of megakaryocytes

Bone Marrow Examination

How well did you know this?

Not at all

Perfectly

INCREASED PLATELET DESTRICTION

IDIOPATHIC THROMBOCYTOPENIC PURPURA
DRUG-UNDUCED IMMUNE THROMBOCYTOPENIA
NEONATAL ALLOIMMUNE/ISOIMMUNE NEONATAL THROMBOCYTOPENIA (NAIT)
NEONATAL AUTOIMMUNE THROMBOCYTOPENIA
POST-TRANSFUSION PURPURA

How well did you know this?

Not at all

Perfectly

IMMUNE MECHANISM OF PLATELET DESTRUCTION

A. Acute and Chronic ITP
B. Drug Induced immunologic
C. Heparin Induced Thrombocytopenia
D. Neonatal Alloimmune (isoimmune neonatal)
thrombocytopenia
E. Posttransfusion isoimmune thrombocytopenia
F. Secondary autoimmune thrombocytopenia

How well did you know this?

Not at all

Perfectly

IDIOPATHIC THROMBOCYTOPENIC PURPURA

ACUTE/CHILDHOOD ITP
CHRONIC/ADULT ITP

How well did you know this?

Not at all

Perfectly

• A.K.A immune thrombocytopenic purpura (ITP)
• One of the MOST COMMON disorders causing ___________________.
• Caused by an ____________ to the patient’s platelet.
• No specific test to confirm presence of ITP rather diagnosis of exclusion.
• Can be present in _______ and _______.

IDIOPATHIC THROMBOCYTOPENIC PURPURA
severe isolated thrombocytopenia
autoantibody
children and adults

How well did you know this?

Not at all

Perfectly

is caused by either immunologic response or by mechanical damage.

Thrombocytopenia

How well did you know this?

Not at all

Perfectly

• ____________ may present with an immune
thrombocytopenia that typically develops acute with a 1-3 weeks duration, usually with bruising or petechiae.
• Present an initial platelet count of ___________________.
• _________, spontaneous remissions with or without therapy in majority of the patient.
• _____________________ and _______________ are often used to decrease the period of thrombocytopenia. IVIG
- _____ – Blocks the immune system from
attacking your own platelets
- Helps to create extra antibodies that will only
last for several weeks or months
• BT _________; PT and APTT – ________

ACUTE/CHILDHOOD ITP
Young children
less than 20 X 109/L
Self-limiting
Intravenous immunoglobulin (IVIG) and corticosteroids
IVIG
prolonged
normal

How well did you know this?

Not at all

Perfectly

• Commonly presents in the ________________, chronic disease process with a greater predilection for women. • Occasionally, patients will have immune ________________________. • Platelet counts are typically _________________ in patients who present with bleeding manifestations. • Patient present with mucosal bleeding typical of a primary hemostatic defect, such as ___________, __________, _____________, or _________. • Does not usually remit spontaneously. • _____ treatment of choice, ___________ as management as well

- CHRONIC/ADULT ITP - 20-50-year-old groups - thrombocytopenia after a viral illness or exposure to drugs - less than 30 X 109 /L - menorrhagia, epistaxis, easy bruisability, petechiae - IVIG - splenectomy

Common Clinical Findings:

• BM is characterized by an increased or normal numbers of megakaryocytes. • Platelet lifespan is shortened and circulating platelets are morphologically large on the smear. • Bleeding time may not be as prolonged as the bleeding time in other disorders associated with the same degree of thrombocytopenia • Measurement of antibodies (IgG) specific for platelet surface GP IIb//IIIa and Ib/IX may provide greater specificity but still are not diagnostic. • Splenectomy and corticosteroids (suppress immune system) are the conventional therapies

• _______ has been recognized as one of the most frequent causes of drug-induced thrombocytopenia; where it acts as a hapten. • Drug most frequently cited: _______, _________, ___________, ___________ and __________ • Appears more frequently in the _______ due to increased usage of medication. • Purpura occurs _________________ of the drug but may occur within 3-5 days owing to anamnestic response.

- DRUG-UNDUCED IMMUNE THROMBOCYTOPENIA - Quinine - Quinine, Quinidine, Salicylates, Sulfa Drugs and Thiazides - elderly - approximately 7 days after initial use

• It results to from immunization of the mother by fetal platelet antigen and placental transfer of maternal antibody - Happens when the mother lacks platelet specific antigen. • It is MOST OFTEN CAUSED by material alloantibodies to ____________. • It is ____________, generally affecting the firstborn child. • Infants who develop this disorder appear normal at birth but within a few hours develop scattered petechiae and purpuric hemorrhages, with platelet counts _____________.

- NEONATAL ALLOIMMUNE/ISOIMMUNE NEONATAL THROMBOCYTOPENIA (NAIT) - P1 ª¹ antigen - uncommon disorder - below 30 X 10^9/L

• Passive transplacental transfer of antibodies from mother with ____ or ____. • Maternal disease severity and/or platelet count during pregnancy can be used to predict the neonatal platelet count in most cases, but the clinical manifestations are _______ than in NAITP. • Affected newborns – normal – __________ platelet numbers at birth (1 week) dec. • Neonatal Thrombocytopenia persist for _______________. • Requires no treatment • If severe Thrombocytopenic infants– IVIG treatment • Bleeding – ____________, ____________, and _____________

- NEONATAL AUTOIMMUNE THROMBOCYTOPENIA - ITP or SLE - less severe - decreased - 1-2 weeksmonths - Platelet Transfusion, IVIG treatment and corticosteroid

• Rare disorder • Develops 1 week after transfusion of _______________. • Manifested by __________ of severe thrombocytopenia –bleeding • _____________ – effective in resolving bleeding • ________ – Tx of choice

- POST-TRANSFUSION PURPURA - platelet containing products - rapid onset - Plasmapheresis - IVIG

QUANTITATIVE PLATELET DISORDER SECONDARY (NON-IMMUNE)

A. Thrombocytopenia in Pregnancy B. HIV Infection C. HDN D. TTP E. DIC F. Drug Induced

THROMBOCYTOPENIA IN PREGNANCY AND PREECLAMPSIA

- HELLPS SYNDROME - GESTATIONAL THROMBOCYTOPENIA

• Incidental Thrombocytopenia of Pregnancy, Pregnancy Associated Thrombocytopenia (PAT), Gestational Thrombocytopenia • Platelet count: ___________________ • Maternal Platelet __________ within several weeks

- THROMBOCYTOPENIA IN PREGNANCY AND PREECLAMPSIA - 100,000 -150,000/ul - returns to normal

Defined by hypertension and proteinuria; usually becomes evident during 2nd trimester and is a major contributor to maternal and fetal morbidity and mortality

PREECLAMPSIA

Defined by the occurrence of acute neurologic abnormalities in a preeclamptic woman during peripartum period.

ECLAMPSIA

• Management: ___________ • Connection with thrombocytopenia, in a manner that blood coagulation is activated and is detected by elevated ___ and _____________ process • Low level of __________ is detected.

- Stat cesarean section - FDG and thrombin-antithrombin - ADAMTS13

• Disorder related to preeclampsia/eclampsia and is seen in the peripartum period and defined by the presence of ____________ (hemolysisanemia), elevated liver enzymes, and low platelet count • HELLP (__________________________) • HELLP is difficult to differentiate from: - _______ - _______ - _______

- HELLPS SYNDROME - microangiopathic HA - (hemolysis, elevated liver enzymes, low platelet count) - TTP - DIC - HUS

• Mild thrombocytopenia with platelet counts of _________ • Commonly develops in the ____________ of pregnancy and does not cause bleeding in the mother or infant. • Low platelet count ______________________.

- GESTATIONAL THROMBOCYTOPENIA - 50- 80 X 109 /L - 3rd trimester - returns to normal after delivery

• Appears to be correlated between ____________, viral load in plasma and the occurrence of thrombocytopenia. • Viral infection of hematopoietic cells, altered marrow microenvironment of dysfunction of the RES contribute to ineffective thrombopoiesis in HIV-related thrombocytopenia. • Development of marrow fibrosis and marrow involvement by AIDS-related lymphoma may also lead to thrombocytopenia • _____________ is often effective course of action. • ______________ and ____________ are found to be effective treatment. • _____________ may be effective but have the potential to increase the risk of infection in immunocompromised individuals • ____________ may also be effective.

- HIV RELATED THROMBOCYTOPENIA - CD4+ T cell depletion - Antiretroviral therapy - Intravenous IgG and anti-D globulin - Corticosteroids - Splenectomy

THROMBOTIC THROMBOCYTOPENIC PURPURA

- ACQUIRED THROMBOTIC THROMBOCYTOPENIC PURPURA (ATTP) - HEREDITARY THROMBOTIC THROMBOCYTOPENIC PURPURA

• First described as a pentad of signs and symptoms that include: 1. _____________ 2. _____________ 3. _____________ 4. _____________ 5. _____________ • ________________ are the characteristic pathologic feature and are found in multiple organs. - Small clots • Coagulation screening tests and D-Dimer assay are NORMAL in TTP, in contrast to DIC which they are ABNORMAL • Two types of TTP: ________ and _________

- THROMBOTIC THROMBOCYTOPENIC PURPURA - Thrombocytopenia - Microangiopathic hemolytic anemia - Fever - Neurologic abnormalities - Renal dysfunction - Hyaline microthrombi - acquired and hereditary

• Thrombi found most extensively in the _____, ________, _______, ________, _________ and _______ and are composed mainly of platelets and vWF. • Associated with __________ (a disintegrinlike and matalloprotease with thrombospodin motifs) and is found in most cases. • ADAMTS13 is also decreased in _______, ____, and ____________

- ACQUIRED THROMBOTIC THROMBOCYTOPENIC PURPURA (ATTP) - heart, pancreas, spleen, kidney, adrenal gland and brain - ADAMTS13 deficiency - sepsis, DIC, and liver desease

LABORATORY FINDINGS

• Thrombocytopenia and hemolysis, with the blood smear showing polychromasia, basophilic stippling, nucleated cells, schistocytes (product of trauma/ fragmentation). • Platelet counts below 20 X 10^9/L at first presentation. • Reticulocyte count increased • Bone marrow studies reveal erythroid hyperplasia, increased number of megakaryocytes and occasionally microvascular hyaline thrombi • Screening tests are usually normal and FDP may be slightly increased • Serum lactic dehydrogenase (LDH) and unconjugated concentrations are common but invariably increased • Hemolysis is of the intravascular type: haptoglobin levels are reduced and hemoglobinuria and hemosiderinuria usually are present • LDH levels and platelet counts are sensitive indices of the response of the disorder to therapy; • Proteinuria and microscopic hematuria are present in most cases • Blood urea nitrogen (BUN) and creatinine are normal or slightly elevated • Liver function tests are usually normal • Analysis of the cerebrospinal fluid is rarely indicated but may reveal an increased protein concentration and xanthochromia • ADAMTS13 binding IgG is detectable enzymelinked immunoabsorbent assay (ELISA) in 97-100% TTP cases

• Also known as _____________ or ___________ • Rare disorder believed to __________________. • In the typical cases, the affected neonate is born with meconium stain or presents within a few hours after birth with ____________, _________ and _____________. • Hemolysis with schistocytes on blood smears may be noted. • Hereditary TTP responds to _____________ per kilogram of body weight administered every 2 to 3 weeks

- HEREDITARY THROMBOTIC THROMBOCYTOPENIC PURPURA - Schulman-Upshaw syndrome or Chronic Relasping TTP - < 1% of the TTP cases - neonatal distress, jaundice and thrombocytopenia - 10-15 mL of FFP

• DIC appears to be accelerated platelet destruction in combination with coagulation factors consumption. • 2 Forms of DIC: 1. ______ – rapid platelet consumption 2. ______ – low grade consumptive coagulopathy • Caused by many illnesses, sepsis, obstetric emergencies and severe trauma, and may cause bleeding. • Chronic form may be seen in cancer and may result in __________ rather than bleeding. • _________________ is usually seen in acute DIC • Platelet count may be normal or elevated in chronic DIC. • Best management is to ___________________

- DISSEMINATED INTRAVASCULAR COAGULATION - Acute - Chronic - thrombosis - Thrombocytopenia - treat the underlying primary cause

ABNORMALITIES IN DISTRIBUTION OR DILUTION

• Splenic Sequestration • Kasabach Merritt Syndrome • Hypothermia • Loss of Platelets: Massive Blood Transfusion

• May lead to thrombocytopenia by inducing a reversible pooling up to _________________. • Platelet production is __________. • Chronic liver disease with portal hypertension and congestive splenomegaly. • MOST COMMON DISORDER CAUSING THROMBOCYTOPENIA.

- SPLENOMEGALY - 90% of total body platelets - usually normal

It is distinguished from uncomplicated splenomegaly in that pooling is accompanied by increased destruction of platelets, leukocytes and erythrocytes in association with increased marrow precursors of the deficient and correction of the cytopenia by splenectomy.

HYPERSPLENISM

• Profound thrombocytopenia related to platelet trapping within a vascular tumour, either a ______________________ or a ________________. • Thrombocytopenia is usually severe and associated with ______. • Contributing factors include “______________” and platelet consumption associated with DIC. • Platelet trapping demonstrated by immunohistochemical staining of the tumors with anti-CD61 antibodies. • Diagnosis: ______________________ • Treatment: _______________________

- KASABACH-MERRITT SYNDROME (HEMANGIOMA) - Kaposi-like hemangioendothelioma or tufted angioma - DIC - platelet trapping - MRI, CT scan, biopsy of tumor - Platelet transfusion, FFP transfusion

• Characterized by an increased in the circulating platelet counts greater than 450,000/uL

THROMBOCYTOSIS

• The result of primary bone marrow disorder. It is characterized by an increase number of platelets which is a result of ________________ that affects all hematopoietic cells. • Patients have bleeding tendencies because of ___________________. • It is most commonly seen in patients with the following disorders: - - - - -

- PRIMARY/ESSENTIAL THROMBOCYTOSIS - clonal proliferation - platelet function abnormalities - Hodgkin’s disease - Polycythemia vera - Myelofibrosis - CML - Thrombocythemia

• A secondary response most associated with the following disorders: 1) 2) 3)

- REACTIVE/SECONDARY THROMBOCYTOSIS - IDA associated with chronic blood loss - Chronic inflammatory disease may be associated with high platelet counts. - Splenectomy-associated thrombocytosis

• Which may occur after a platelet depletion through a massive blood loss. • _______ in plasma are decreased. • Promoted by different types of drugs like _____________, __________________

- REBOUND THROMBOCYTOSIS - TPO levels - epinephrine, recombinant IL11 (Oprevelkin)

CLINICAL MANIFESTATIONS OF BLEEDING DISORDERS:

- Superficial bleeding - Deep Tissue Bleeding

Superficial bleeding

- Petechiae - Epistaxis - Gingival Bleeding

Deep Tissue Bleeding

- Hematomas - Hemarthrosis

QUALITATIVE PLATELET DISORDER: CONGENITAL DISORDERS OF PLATELET FUNCTION

- PLATELET MEMBRANE DEFECTS - PLATELET RELEASE (SECRETION DEFECTS) - PLATELET COAGULANT DEFECT - VON WILLEBRAND’S DISEASE

PLATELET MEMBRANE DEFECTS

• Glanzmann’s Thrombasthenia • Bernard-Soulier Syndrome • Storage Pool Deficiency (Granule Defect)

• Primary Secretion Defect (enzymatic pathway defects)

PLATELET RELEASE (SECRETION DEFECTS)

• Defects in platelet-vessel wall interaction

PLATELET ADHESION DEFECTS

• Rare autosomal recessive disorder • Defect in a quantitative decrease or abnormal function of ____________ • Characterized by giant platelets and mild thrombocytopenia • Platelets on smear ranges from ______________________. - Sometimes called as Giant Platelet Syndrome • Platelets adhesiveness test is abnormal • An inherited disorder of the platelet GPIb/IX/V complex characterized by thrombocytopenia, giant platelets, and a failure of the platelets to bind GPIb ligands (von Willebrand’s factor and thrombin) • In 1948, _______ and _________ described two children from a consanguineous family who had a severe bleeding disorder characterized by mucocutaneous hemorrhage. • In 1975, _______________ identified an abnormality in platelet GPIb as the cause of functional defect.

- BERNARD-SOULIER SYNDROME - GPIb/IX complex - 5 to 8 um up to 20 um - Bernard and Soulier - Nurden & Caen

Six different features may contribute to the hemorrhagic diathesis:

1. Thrombocytopenia 2. Von Willebrand’s Factor 3. Abnormal platelet interactions with thrombin 4. Abnormal platelet coagulant activit 5. Abnormal platelet interactions with P-selectin, and 6. Abnormal platelet interactions with integrin αMβ2

• ____________ is the most common symptom (70%); also are ecchymoses (58%), menorrhagia (44%), gingival hemorrhage (42%), and gastrointestinal bleeding (22%)

Epistaxis

LABORATORY FEATURES: • ______ – normal responses to ADP, epinephrine, collagen, and arachidonic acid • Do not respond to: _______ and _______ - ________ – used to treat staphylococcal infection

- BSS - Ristocetin and Thrombin - Ristocetin

TREATMENT:

• No specific treatment • Platelet transfusion – therapy of choice – (alloabs) - When bleeding is present, platelet transfusion can be performed. However, there’s a risk that there will be a production of alloantibodies.

• Defects in platelet – platelet interaction

PLATELET AGGREGATION DEFECTS

• ___________________ – deficiency in GPIIb/IIIa complex • ________________, a swiss pediatrician, described a group of patients with hemorrhagic symptoms and a defect on platelet function (weak platelet or thrombasthenia) • Bleeding is ___________________ (easy bruisability, epistaxis, gingival bleeding, prolonged bleeding for minor cuts, and menorrhagia) • Facial petechiae and subconjunctiva hemorrhages seen in infants ____________ • Deep hematoma formations and recurrent hemathroses ___________ • Originally - bleeding disorder associated with abnormal in vitro clot retraction and normal platelet count. • Hemorrhagic Manifestation: - petechiae, purpura, menorrhagia, GIT bleeding and hematuria.

- GLANZMANN THROMBASTHENIA - Rare autosomal recessive disease - 1918, Eduard Glanzmann - most common from mucosal surfaces - associated with crying - are not present

LABORATORY FEATURES:

• Normal: Platelet count, platelet morphology • Lack of platelet aggregation in response to all platelet activating agent. ADP, collagen, thrombin, and epinephrine.

TREATMENT:

• Transfusion of platelet • Recombinant factor VIIa

INHERITED GIANT PLATELET DISORDERS

1) BSS 2) Giant Platelets with Velocardiofacial syndrome 3) Giant platelets with abnormal surface glycoproteins and mitral valve insufficiency 4) Familial macrothrombocytopenia with GP IV abnormality 5) Montreal Platelet Syndrome 6) May-Hegglin Anomaly 7) Mediterranean Macrothrombocytopenia 8) Fechtner Syndrome 9) Sebastian Syndrome 10) Hereditary Macrothrombocytopenia • Epstein Syndrome • Gray Platelet Syndrome

• Originally described as ______________. • Early onset description of this autosomal dominant disorder includes severe bleeding after trauma, mild thrombocytopenia, decreased functional Platelet Factor 5 and normal plasma Factor V. • Diagnosis can be established by analysis of platelet urokinase-type plasminogen activator or the identification of degraded granule proteins by immunoblot analysis. • Because the PF5 abnormality is prominent, this defect may also be classified as defect in platelet coagulant activity.

- QUEBEC PLATELET DISORDER - Factor V Quebec

• Relatively _______ and _________ of macrothrombocytopenia and has been described in a group of healthy subjects from Italy and the Balkan peninsula. • An _____________________________ • Gene mutation to the short arm of chromosome ________ • Genotype and phenotype are equivalent to that of carrier of ___________________. • Patients have mild bleeding diathesis; PBS shows platelets that are larger than normal.

- MEDITERRANEAN MACROTHROMBOCYTOPENIA - common and mild form - Autosomal Dominant Thrombocytopenia - 17 (GP Ia) - Bernard-Soulier syndrome

PLATELET STORAGE POOL DISEASE

• Dense Granules Deficiency • Hermansky Pudlak Syndrome • Chediak Higashi Syndrome • Wiskott Aldrich Syndrome • TAR Syndrome • Alpha Granule • Gray platelet syndrome

• An autosomal recessive disorder characterized by a severe deficiency of _____________. • Patients show ________ (oculocutaneous) and may have ________________. • Defective lysosomal function. • The gene is located on ______________. • Also known as albinism with hemorrhagic diathesis. • Marked dilation and tortuosity of the surface connecting tubular system (swiss cheese platelet) • Most bleeding in HPS is not severe • Diagnosis: - ________________ - ________________

- HERMANSKY-PUDLAK SYNDROME - dense granules - albinism - hemorrhagic events - chromosome 19 - Examining the platelet - Genetic screening

• An ___________________, in which patients show albinism and giant lysosomal granules in neutrophils. • Storage pool defect on ________________. • Patients show ______________ because of impaired phagocytic ability and death usually occurs in childhood. • Patients manifest thrombocytopenia • Partial oculocutaneous albinism • Platelet dense granule deficiency and hemorrhages. • Decreased or no melanin. • Gene mutation: _____________

- CHEDIAK-HIGASHI SYNDROME - autosomal recessive disorder - dense granules - frequent infections - Chromosome 13

• An ______________ in which patients show severe eczema, recurrent infections, immune defects, thrombocytopenia and small platelets. • Death from ________, _________ or __________ is common before adulthood. • A defect in the ________________ (CD43, gp115, leukosialin) has also been described in WiskottAldrich syndrome. • It is combination of ineffective thrombocytopoeisis and decreased of platelet sequestration. • Number of dense granules decreased • WAter – ___________________________________

- WISKOTT-ALDRICH SYNDROME - X-linked recessive disorder - infection, hemorrhage or malignancy - surface glycoprotein sialophorin - Wiskott-Aldrich, thrombocytopenia, eczema, recurrent infections

• Autosomal recessive • It is associated with ______________ and ___________________. • ____________ are absent or greatly reduced. • Absence of alpha-granules, one of the results is a continued leakage of growth factors and cytokines into the marrow, causing ___________. • Lifelong mild bleeding, large platelets, thrombocytopenia

- GRAY PLATELET SYNDROME - bleeding tendencies and classical abnormal platelet morphology - α-granules - myelofibrosis

TREATMENT

• If severe bleeding: platelet transfusion • If the bleeding is uncontrollable: cryoprecipitate • Desmopressin (DDAVP) – to shorten the bleeding

ACQUIRE DEFECTS OF PLATELET FUNCTION

• Drug Induced Defects • Myeloproliferative Neoplasm • Multiple Myeloma - Waldenstrom Macroglobulinemia - Liver Disease - Uremia

• Include Polycythemia Vera (PV), idiopathic myelofibrosis, CML, and essential thrombocythemia. • Hemorrhagic manifestations include: epistaxis, ecchymosis and mucocutaneous bleeding from ____ and ___. • Thrombosis includes DVT, pulmonary embolism, stroke, MI, and thrombosis of the hepatic, portal, splenic and mesenteric veins. • Laboratory abnormalities include: - Abnormal release and aggregation in response to __________, _______ and ____. - Bleeding time is prolonged in most cases but does not correlate to bleeding tendencies. • Other abnormalities include: - Acquired storage pool defects, abnormal prostaglandin and arachidonic acid metabolism, and - Platelet hyperactivity

- MYELOPROLIFERATIVE DISORDERS - GIT and GUT - epinephrine, collagen and ADP

• Abnormalities include decrease in platelet number and function, factor deficiencies resulting from _________ and _________, increased fibrinolytic activity, DIC and inadequate or excess neutralization of heparin or protamine. • During the bypass, a prolonged bleeding time can be seen in a mildly low platelet count _______________. • _____________ and ___________ account for the bleeding complications • Platelet concentrates are administered to _______________. • FFP and cryoprecipitate should be given only to treat bleeding associated with _________________.

- CARDIOPULMONARY BYPASS - consumption and hemodilution - (100 X 109 /L) - Platelet activation and platelet dysfunction - stop bleeding - coagulation factor deficiency

• Associated with multiple __________________ and other related malignant paraprotein disorders. • Hemostatic abnormalities to be caused by interaction of the paraprotein with platelets and coagulation factors. • _______________ is characterized by a prolonged bleeding time and platelet dysfunction. • Patients may present spontaneous epistaxis and ecchymosis, or unexplained postoperative bleeding in the face of a normal platelet count and coagulation profile. - Platelets are coated with proteins = nonfunctional • Platelet abnormalities include decreased aggregation in response to various aggregating agents, altered shape change, abnormal release reactions, and a prolonged bleeding time. • THERAPY: ________________ to reduce the circulating paraprotein concentrations and chemotherapy to inhibit paraprotein production.

- PARAPROTEINEMIA - myeloma, Waldenström’s macroglobulinemia, - Hemorrhagic diathesis - Plasmapheresis

• Associated with significant ______________ as a result of platelet dysfunction. • Mild to moderate ________________ is seen as a result of splenic sequestration secondary to congestive splenomegaly. • Reduced platelet adhesion; abnormal platelet aggregation to ADP, epinephrine & thrombin; and abnormal PF3 availability. • __________________________ is helpful. • ________ may improve the qualitative defect. • _______________ may decrease the over-all bleeding tendency after an acute episode.

- LIVER DISEASE - hemorrhagic diathesis - thrombocytopenia - Transfusion with Platelet Concentrate - DDAVP - Conjugated estrogens

• __________ is a common complication. • Petechiae, purpura, epistaxis, ecchymosis and GIT bleeding are common. • Abnormality in the interaction of vWF and platelet GPIIb/IIIa complex; however, _____________________ • Other platelet abnormalities: abnormal prostaglandin synthesis, decrease membrane procoagulant activity, decreased platelet serotonin release, abnormal βthromboglobulin levels, elevated intracellular calcium and decreased TX synthesis. • Increased levels of uremic toxins such as _____________ and __________. • Mild thrombocytopenia _____________, decreased adhesion, abnormal aggregation and increased bleeding time.

- UREMIA - Bleeding - GPIb, GPIIb and GPIIIa are quantitatively normal. - guanidosuccinic acid and phenols - (100 X 109 /L)

TREATMENT

• EPO (r-HuEPO) effective in improving, hemostasis and decreasing bleeding tendencies. - Increase the hematocrit to 30% to normalize the bleeding. • Hemodialysis or peritoneal dialysis is the treatment of choice to correct the hemostatic defect

Disorders of Primary Hemostasis (Platelet Disorders) Flashcards

(85 cards)