Chapter 140 - Disorders of Platelets and Vessel Wall Flashcards Preview

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Flashcards in Chapter 140 - Disorders of Platelets and Vessel Wall Deck (52):
1

"Genetic and acquired influences on the platelet and vessel wall, as well as on the coagulation and fibrinolytic systems, determine whether normal hemostasis or bleeding or clotting symptoms will result."
True or False?

True.

2

Which hormone is the major regulator of platelet production?

Thrombopoietin (TPO).

3

How much mass of the platelets reside within the spleen? How low can be the platelet count due to an enlarged spleen?

"Approximately one-third of the platelets reside in the simple, and this number increases in proportion to splenic size, although the platelet count rarely decreases to less than 40 000/uL"

4

Von Willebrand Factor (vWF) is exposed in the subendothelium when there is damage to the vessel wall but there is also plasmatic vWF.
True or False?

True.

5

What are the major components of the platelet granules?

"Activated platelets undergo release of their granule contents, which include nucleotides, adhesive proteins, growth factors, and procoagulantes that serve to promote platelet aggregation and blood clot formation and influence the environment of the forming clot."

6

How many endothelial cells do we have in our circunlatory tree?

1-6 x 10 to the 13, which is "enough to cover a surface area equivalent to about six tennis courts."

7

Name the primary vasodilator and vasoconstrictor secreted by the endothelium and name, if applicable, their hemostatic functions.

Nitric oxid is secreted by the endothelium and is the most important vasodilatador which also functions as a platelet inhibitor. Conversely, endothelin is the major vasocontritor secreted by the endothelium which also functions as a platelet activator.

8

What are the 3 major processes that lead to thrombocytopenia?

"(1) decreased bone marrow production; (2) sequestration, usually in an aenlarged sleen; and/or (3) increased platelet destruction."

9

What is the explanation for pseudothrombocytopenia and how can you differentiate from true thrombocytopenia?

"Pseudothrombocytopenia is an in vitro artifact resulting from platelet agglutination via antibodies (usually IgG, but also IgM and IgA) when the calcium content is decreased by blood collection in ethylenediamine tetraacetic (EDTA) (...) If a low platelet count is obtained in EDTA-anticoagulated blood, a blood smear should be evaluated and a platelet count determined in blood collected into sodium citrate (blue top tube) or heparin (green top tube), or a smear of freshly obtained unanticoagulated blood, such as from a finger stick, can be examined."
The blood smear will reveal platelet clumping in pseudothrombocytopenia.

10

What is the first step in evaluating a patient with thrombocytopenia?

It is fundamental to evaluate the hemoglobin and white blood count. "Except in unusual inherited disorders, decreased platelet production usually results from bone marrow disorders that also affect red blood cell (RBC) and/or white blood cell (WBC) production)."

11

In a patient older than 60 year old of age that presents with isolated thrombocytopenia, what might be an important evaluation?

"Because myelodysplasia can present with isolated thrombocytopenia, the bone marrow should be examined in patients presenting with isolated thrombocytopenia who are older than 60 years of age."

12

What is the most sensitive bedside technic that can evaluate splenomegaly?

Abdominal ultrassonography.

13

Name three important findings in patients with thrombocytopenia that denote an increased risk of life-threatening hemorrhage.

Wet purpura, blood blisters and retinal hemorrhage.

14

How different might be the cell blood count in a patient with early versus late HIV infection?

A patient with early HIV might present with isolated thrombocytopenia. On the other hand, late HIV presents with pancytopenia (anemia is almost always present) and the platelets are dysplatic.

15

When is it that invasive testing in HIV-infected patients with fever of unknown origin are recommended?

"a bone marrow examination and culture are recommended when the diagnosis is needed urgently or when other, less invasive methods have been unsuccessful."

16

Which group of drugs induce thrombocytopenia in a dose-dependent manner?

Chemotherapeutic drugs in general, for example.

17

What are the most frequent drugs that can induce classsic drug-dependent antibodies?

Quinine and Sulfonamides.

18

How different in timing is the thrombocytopenia induced by classic drug-dependent antibodies, abciximab and heparin?

Classic drug-dependent antibodies lead to thrombocytopenia after a period of initial exposure with a median of 21 days, resolving 7-10 days after drug withdrawal. Abciximab might induce thrombocytopenia within 24 h of initial exposure. Heparin-induced thrombocytopenia (HIT) might occur affter exposure to heparin for 5-14 days, occuring before 5 days in those who were exposed in the last ~100 days and occuring rarely after 14 days as a form of delayed-onset HIT.

19

What is the difference between ELISA and platelet activation assay in the study of heparin-induced thrombocytopenia?

ELISA is more sensitive but less specific, namely because it detects the antibodies anti-heparin/PF4), which might occur in asymptomatic patients. The platelet activation assay is more specific but less sensitive since it measures the ability of the patient's serum to activate platelets in the presence of heparin.

20

What is the major consequence of heparin-induced thrombocytopenia?

Thrombosis.

21

What are the FDA-approved anticoagulants for heparin-induced thrombocytopenia?

Direct thrombin inhibitors argatroban and lepirudin. "The DTI bivalirudin and the antitrhombin-binding pentasaccharide foundaparinux are also affective but not yet approved by the U.S. Food and Drug Administration (FDA) for this indication."

22

What are differences of timing of therapy with warfarin between heparin-induced thrombocytopenia with and without thrombosis?

"In patients with thrombosis, patients can be transitioned to warfarin, with treatment usually for 3-6 months. In patients without thrombosis, the duration of anticoagulation needed is undefined. An increased risk of thrombosis is present for at least 1 month; however, most thromboses occur early, and whether thrombosis occur later if the patient is initially anticogulated is unknown. Options include continuing anticoagulation until a few days after platelet recovery or for 1 month."

23

What are the risks of warfarin in heparin-induced thrombocytopenia (HIT)? How is it possible to mitigate those risks?

Warfarin is initially prothrombotic, summing itself to the prothrombotic risk of HIT. Therefore, it might precipitate thrombosis, particularly venous gangrene.
"Warfarin, if started, should be overlapped with a Direct Thrombin Inhibitor or fondaparinux and started after resolution of the thrombocytopenia and lessening of the prothrombotic state."

24

Name major causes of secondary Immune Thrombocytopenic Purpura.

Autoimmune diseas, such as Systemic Lupus Erythematosus, and infectious, such as HIV and hepatitis C.

25

What are the laboratory findings in Evans syndrome?

Autoimmune hemolytic anemia with Immune thrombocytopenic purpura.

26

What are the possible infrequent side effects of intravenous gamma globulin (IvIgG)?

"Side effects are usually related to the volume of unfusion and infrequently include aseptic meningitis and renal failure."

27

What are the treatments available for Immune thrombocytopenic purpura?

Rh0(d) immune globulin, intravenous gamma globulin, rituximab, splenectomy and TPO agonists.

28

What TPO agonists are available? How are the administered?

Romiplostim, subcutaneously.
Eltrombopag, orally.

29

What is the gene now known to be involved in cases of autossomal dominant inherited thrombocytopenia?

MYH9 gene, which encodes for the nonmuscle myosin heavy chain.

30

Name one syndrome responsible for thrombocytopenia inherited in a X-linked fashioned way.

Wiskott-Aldrich syndrome.

31

What conditions are associated with MYH9 mutations?

May-Hegglin anomaly, and Sebastian, Epstein's and Fechtner syndromes.

32

What is the main laboratory finding difference between disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS)?

DIC is associated with elevation of prothrombin time and often of activated partial thromboplastin time. These times are normal in both TTP and HUS.

33

What is the protein deficiency, quantitative or qualitative, that is mostly associated with thrombotic thrombocytopenic purpura (TTP)? How might it explain the pathogenesis of TTP?

ADAMTS13.
"VWF is normally secreated as ultra-large multimers, which are then cleaved by ADAMTS13. The persitence of ultra-large VWF molecules is thought to contribute to pathogenic platelet adhesion and aggregation."
"ADAMTS13 activity levels of

34

What are the drugs associated with microangiopathic hemolytic anemia?

"(...) may be secondary to antibody formation (ticlopidine and possibly clopidogrel) or direct endothelial toxicity (cyclosporin, mitomycin C, tacrolimus, quinine)."

35

What is the mainstay of treatment for thrombotic thrombocytopenic purpura?

Plasma exchange.

36

What are the mortality rates associated with hemolytic-uremic syndrome?

Less than 5% versus 26%, for typical versus atypical hemolytic-uremic syndrome, respectively.

37

Name the mechanisms responsible for thrombocytosis.

"(1) iron deficiency; (2) inflammation, cancer, or infection (reactive thrombocytosis); or (3) an underlying myeloproliferative process (essential thrombocythemia or polycythemia vera)."

38

What is the major consequence of thrombocytosis?

Risk of bleeding, in part due to acquired von Willebrand disease due to platelet-VWF binding and removal from the circulation.

39

Which glycoproteins are absent in Glanzmannm's thrombasthenia and Bernard-Soulier syndrome?

Gp IIb/IIIa and Gp Ib/IX/V, respectively.

40

Name a syndrome responsbile for disorders of granule formation of the platelets.

Hermansky-Pudlak syndrome.

41

What is the main treatment for mucosal bleeding in inherited disorders of platelet dysfunction?

Anti-fibrinolytic agents such as epsilon-aminocaproic acid or tranexamic acid.

42

Name the different types of von Willebrand Diseases.

Type 1
Type 2 - 2A, 2B, 2M, 2N
Type 3

43

What blood type is associated with lower levels of von Willebrand Factor proteins?

0 blood type.

44

Which type 2 von Willebrand Disease is associated with a mutation that is responsible for gain-of-function?

Type 2B.

45

How come gain-of-function of von Willebrand Factor induces risk of bleeding instead of thrombosis?

"Type 2B VWD results from gain-of-function mutations that result in increased spontaneous binding of VWF to platelets in circulation, with sbusequent clearence of this complex by the reticuloendothelial system. The resulting VWF in the patients' plasma lacks highest molecuylar-weight multimers, and the platelet count is usually modestly reduced."

46

What is the disease also known as autosomal hemophilia?

Type 2N Von Willebrand Disease. This type is due to mutation in von Willebrand Factor that afect its binding to factor VIII. Therefore, the half-life of FVIII is reduced and, consequently, its levels are markedly reduced. In conclusion, this disease is similar to hemophilia A, although factor VIII is normally produced.

47

Name the disease more associated with acquired Von Willebrand Disease.

"Acquired VWD is a rare disorder, most commonly seen in patients with underlying lymphoproliferative disorders, including monoclonal gammopathies of undetermined significance (MGUS), multiple myeloma, and Waldesntrom's macroglulinemia. It is seen most commonly in the of MGUS (...)"

48

What is the major adverse effect of the use of desmopressin? Is there any risk groups?

Hyponatremia is the most frequent adverse effect, especially in patients who do not restrict from water intake in the next 24 h. The risk groups include the very young and the very old.

49

Desmopressin might be used preceding minor procedures in patients with von Willebrand Disease type 2A and 2M.
True or False?

True.

50

Easy bruising in old aged is most due to Cushing's syndrome or glucocorticoid therapy.
True or False?

False.
A phenomenon of easy bruising is frequently observed in the elderly due to atrophy of the connective tissue, mostly in the areas previously exposed to the sun. It is called senile purpura.

51

Glucocorticoids are used in Henoch-Schonlein purpura because they reduce morbidity and mortality associated with renal failure.
True or False?

False.
"Glucocorticoids can provide symptomatic relief but do not alter the course of the ilness."

52

Name the mutations associated with Osler-Weber-Rendu syndrome. Which of those are more associated with pulmonary arteriovenous (AVMs) malformations?

Endoglin (eng gene) on chromossome 9q33-34 (type 1), which is associated with pulmonary AVMs in 40% of the cases and activin-receptor-like kinase 1 (gene alk1) on chromossome 12q13.