Chapter 22: Alterations of Hemostasis

the major adverse effects of desmopressin (DDAVP)

facial flushing, headache, tachycardia, hyponatremia

a genetic lack of ________ leads to hemophilia

factor VIII

the formation of thrombocytes is referred to as ______ or ________

megakaryocytopoiesis or thrombopoiesis the megakaryocyte is the earliest identifiable cell in the pathway to platelet production

Thrombocythemia

excess of platelets that lead to a spontaneous blood clot formation

thrombocytopenia can result from 4 pathophysiologic processes. list the 4 and explain.

1. artifact: pseudothrombocytopenia/ false thrombocytopenia- the usual cause is platelet clumping secondary to the use of an anticoagulant called ethylenediamineteraacetic acid that results in incorrect conunting of platelets. usually occurs in 1 in 1000 cases and generally has no clinical significance. 2. deficient platelet production: results from processes that affected the bone marrow and produce marrow aplasia 3. increased destruction and/or consumption of platelets - increases destruction of platelets is the mechanism involved in immune thrombocytopenic purpura (ITP). this disease involves destruction of platelets by antiplatelet antibodies, resulting in decreased platelet survival rate. 4. abnormal distribution or pooling of platelets- uncomplicated splenomegaly or hypersplenism my lead to thrombocytopenia by inducing a reversible pooling of up to 90% of the total body platelets.

5 clinical manifestations of TTP

1. microangiopathic hemolytic anemia 2. thrombocytopenia 3. renal insufficiencies 4.fever 5. mental status changes that can wax and wane (confusion, headache, fatigue, seizures, strokelike syndrome) *Not all 5 clinical manifestations are always seen; the complete pentad is found in only about 40% of individuals and is a late finding that is associated with a poor outcome*

another way to view hemostasis is a set of reactions leading to formation of a blood clot when a blood vessel is injured or damaged. this process has three primary steps or phases. list them.

1. vascular phase - injury to a blood vessel causes a reactive constriction or spasm of the blood vessel. afterward, platelets are activated and travel to the site of injury 2. aggregation phase - the platelets begin to clump together to form a dam or plug 3. coagulation phase - platelets release immune proteins and other factors, leading to the formation of fibrin, which forms a layer over the platelet plug to help stop blood loss **alternative approach to the naming of these phases** 1. initiation 2. amplification 3. propagation

the normal range of circulating platelets is approximately

150,000-450,000/µL. there is an increased risk of bleeding rarely occurs until there are fewer than 80,000 -100,000/µL. there is a particularly high risk of spontaneous bleeding once the count drops below 10,000/µL

Disseminated Intravascular Coagulation (DIC)

A life- threatening condition in which the protein that control clotting become overreactive. sepsis, shock, and trauma are known to trigger DIC.

there are two main pathways involved in coagulation __________ and ____________. the pathways involved share certain factors and the shared components are referred to as the common pathway

INTRINSIC and EXTRINSIC the presence of blood outside the circulatory system stimulates the release of tissue factor from cells that are normally no directly in contact with circulating blood, such as fibroblast or smooth muscle cells. the release of tissue factor activate the extrinsic pathways. the intrinsic pathway can be activated by the actions of extrinsic particularly through damage in the vascular system. the main protein involved in the pathway is thrombin, which transforms fibrinogen into fibrin.

the development of all blood cells begins with a hematopoietic stem cell. from there the proliferation and differentiation of blood cells are influenced by a number of different growth factors and other immune mediatiors that lead to the hematopoietic stem cell being divided into two different cells: _______ and ________

Lymphoid precursor and myeloid precursor.

thrombocythemia (aka essential thrombocythemia)

a condition characterized by higher than expected numbers of thrombocytes. typically this is defined a an elevated platelet count grated than 600,000/µL.

hemophilia. define the two types

a hereditary genetic bleeding disorder resulting from the loss of select clotting factors. Hemophilia A results from a lack of factor VIII. 1 in 50,000 male births. Hemophilia B results from a deficiency in factor IX. 1 in 30,000 male births. these result from a chromosomal abnormality in which a nonfunctioning form of the related gene is produced. the genes for both factor VIII and factor XI are on the X chromosome; therefor the disease usually affects males.

Thrombocytopenia

a reduction in the number or function of platelets which can lead to spontaneous bleeding (ie. von Willebrand disease).

Hemostasis

a term that refers to cessation of blood flow, particularly through the action of coagulation (clotting) mechanisms

what is the main risk of thrombocytopenia

blood loss; emergent care involves plasma exchange (plasmapheresis). this therapy is designed to aid in reducing the concentration of autoimmune antibodies in the plasma and slowing the destruction of platelets

many proteins that are involved in immunologic defense also play a role in clotting pathways, and thrombocytes secrete a primary ___________ that draws immune cells to the site of injury

chemoattractant protein (interleukin 8)

the two treatment options for spontaneous bleeding episodes are:

desmopressin (DDAVP) and transfusion with plasma- derived vWF products. Desmopressin is used for patients with type 1 vWD and a subset of type 2 vWD. Desmopressin increases vWF levels twofold to fourfold and generates a similar increase in factor VIII. For individuals with type 3 vWD and those with type 2 in whom DDAVP is ineffective or contraindicated, plasma concentrates of factor VIII and vWF are used.

the blood is made up of two main components

plasma (the liquid portion) and blood cells (the formed element). plasma accounts for approximately 55% of the total blood volume. much of the plasma is volume is water (91%) and approximately 8% is plasma proteins including albumin, coagulation factors, immunoglobulins and complement. the remaining is 1% that includes nutrients, electrolytes, vitamins, hormones, waste products, drugs and dissolved gases such as oxygen and carbon dioxide.

hemostasis has either primary or secondary disorders. describe primary vs secondary

primary disorders are associated with abnormalities in the number or function of platelets; secondary disorders are associated with lack of, or reduction in factors tied to coagulation

Fibrin

provides the necessary structures to form a mesh layer which forms a blood clot.... sufficient thrombin is usually present to initiate the intrinsic pathways, which takes over the role of manufacturing fibrin

hemorrhage

refers to copious bleeding, which can be outside the skin (as from a laceration) or in the skin, which is called Ecchymoses (bruising)

factor IX in process of clot formation

the first stage begins with vessel injury and the release of tissue factor. tissue factor then stimulates the release of thrombin, which in turn activates a clotting factor referred to as factor IX. factor IX then propagates clotting through binding of platelets an results in clot formation

plasmin- mediated fibrinolysis

the formation of D-dimers and other components that lead to the breakdown and degradation of fibrin.

what is the megakaryocyte responsible for?

the megakaryocyte is a large cell in the bone marrow that is responsible for the production of thrombocytes (platelets)

thrombopoiesis is regulated by a variety of cytokines and growth factors, including ___________, ____________,___________,__________ and __________

thrombopoietin, IL-3, IL-6, IL-11, and GM-CSF thrombopoietin is the most important protein in the production of platelets. Platelets have receptors for this protein, which increases as platelet numbers decrease as platelets numbers increase. Thrombopoietin stimulates proliferation of progenitor cells and supports differentiation of the megakaryocyte. IL-3 is needed to support the early development of progenitor cells such as the burst forming unit, the megakaryocyte. IL-6 acts in synergy with thrombopoietin to increase numbers of megakaryocytes. IL -11 is elevated in response to low platelet production by acting on both early progenitor cells and in the development of megakaryocytes.

the two types of Heparin- Induced Thrombocytopenia (HIT)

type 1: involves a modest transient decrease in platelet count within the first 2-3 days after initiation of heparin therapy. no clinical significance. type 2: seen in 0.3-0.5% of individuals treated with unfractionated heparin. it is caused by antibodies to platelet factor 4 on the heparin complex. seen about 4- 14 days after initiation of heparin therapy.

list and explain the 3 types of von Willebrand disease.

type 1: occurs in 70-80% of all cases of this disease and is characterized by either a failure to manufacture the factor or increased clearance. usually asymptomatic for a long period of time type 2: there are several variants of type 2 in which the binding ability of the factor is either significantly enhanced or delayed, resulting in functional deficits type 3: a more severe form in which there is a complete absence of production of the factor. presents similar to hemophilia, with life threating clinical manifestations and internal bleeding.

one of the main glycoproteins involved in hemostasis is von Willebrand factor. this factor aids in protein binding, allowing platelets to adhere to points of injury. defects in the genetic expression of this protein leads to the most common bleeding disorder with a genetic cause is known as __________

von Willebrand disease (vWD)