Hemostasis and Related Disorders Pathology Term 3

Glanzmann Thrombasthenia

* * * *

Bernard Soulier Syndrome

* * * * *

Schistocytes

* * * * * *often called *Helmet Cell*

Differentiating Vitamin K deficiency from Vitamin C deficiency

*ADD MORE

Idiopathic Thrombocytopenic Purpura and Neonatal thrombocytopenia

*Autoantibodies, especialy IGG, are able to cross the placenta and attack fetal platelets *The mother has a normal platelet count, while the fetus can be severely thrombocytopenic. *

Idiopathic Thrombocytopenic Purpura

*Caused by the production of IGG autoantibodies to platelets *Results in Destruction of antibody-coated platelets in the spleen *Often follows a viral infection or immunization *acute and self limiting in children after upper resp infectino *typically chronic in adults *females are affected twice as often as males (often during pregnancy) *ITP can be distinguished from other hematologic causes of thrombocytopenia via the absence of fever, splenomegaly, schistocytes on blood smear, and an abnormal PT/PTT. *

Describe the laboratory findings seen in Idiopathic Thrombocytopenic Purpura

*Decreased platelet count < 50000/microL *Normal PT/PTT* *Increased megakaryocytes on bone marrow biopsy*

Vitamin K Deficiency

*Disrupts function of multiple coagulation factors * * * * *

Hemolytic Uremic Syndrome (HUS)

*E Coli verotoxin damages endothelial cells resulting in platelet microthrombi *Occurs most often in children *Typically follows a gastroenteritis (typically due to verotoxin producing E Coli 0157:H7) *Results from exposure to undercooked beef *-Preceding bloody diarrhea may or may not be present. *No Fever unlike TTP* *Both TTP and HUS will present with both renal problems and CNS abnormalities but renal problems are the predominant ones in HUS *HUS in adults does not present with diarrhea* *Increased megakaryocytes in bone marrow biopsy *

Hemophilia A

*Genetic Factor 8 Deficiency *XLR *Predominantly affects males* *Females may be affected due to unequal inactivation (lyonization)* *Can arise from a new mutation without any family history *Hemophilia A is more common than Hemophilia B *Presentation varies in severity based on degree of Factor VIII deficiency*

Von Willebrand Disease

*Genetic vWF deficiency *most common inherited coagulation disorder* *multiple subtypes exist *The various types of vWD present with varying degrees of bleeding tendency, usually in the form of *easy bruising, nosebleeds, bleeding gums, excessive blood loss during pregnancy, heavy menstrual bleeding* *most common type is AD with decreased vWF levels *Abnormal Ristocetin Test* *

Clinical Presentation of Hemophilia A and B

*Hemophilia A and B are clinically indistinguishable* Presentation varies in severity based on degree of Factor VIII deficiency* * * *If bleeding in joints is severe, patients may feel an "abnormal sensation within the joints"

How do you differentiate between Congenital Hemophilia A and acquired Hemophilia (Anti-Factor8)?

*Mixing studies* differentiate between factor deficiency and inhibitor presence an *PTT does NOT correct after mixing normal plasma with patient's plasma (mixing study) due to presence of inhibitor *PTT DOES correct in hemophilia A

How do the manifestations of disorders of secondary hemostasis differ from disorders of primary hemostasis?

*Primary: Superficial Bleeding *Secondary: Deep tissue bleeding into muscles and joints; rebleeding after surgical procedures *Manifestations of Seondary Hemostasis include bleeding from larger vessels,resulting in hemarthroses (blood in joint spaces), large hematomas, large ecchymoses, and extensive bleeding with trauma. *Bleeding time or platelet count is not affected (thus distinguishing secondary hemostatic disorders from primary hemostatic disorders)*

What diseases are associated with Idiopathic Thrombocytopenic Purpura

*SLE* *HIV *Lymphoproliferative disorders*

Thrombotic Thrombocytopenic Purpura (TTP)

*Severe bleeding disorder due to a decrease in ADAMTS13 function *ADAMTS13 most commonly disabled by an autoantibody* *Large uncleaved multimers adhere platelets and form microthrombi* *results in diffuse emboli and thrombi that damage brain and kidneys *Similar to Hemolytic Uremic Syndrome (HUS) *different in that HUS does not involve fever *Most commonly seen in adult female *Increased megakaryocytes in bone marrow biopsy * * * * *

Hemostasis

*a process which causes bleeding to stop, meaning to keep blood within a damaged blood vessel *It is the instinctive response for the body to stop bleeding and loss of blood. *Occurs in two stages; Primary and Secondary * * * *

What symptoms are classically present in Thrombotic Thrombocytopenic Purpura (TTP)?

*classic pentad of symptoms *(FAT RN)* *Fever *microangiopathic hemolytic Anemia *Thrombocytopenia (bleeding, bruising) *Renal dysfunction more pronounced in HUS (recall the name uremic) *Neurologic abnormalities and mental status changes

Microangiopathic Hemolytic Anemia

*pathologic formation of platelet microthrombi in small vessels *Platelets are consumed in the formation of microthrombi *RBCs are sheared as they cross the microthrombi, resulting in hemolytic anemia with schistocytes *Seen in TTP and HUS* *A form of Intravascular Hemolysis* * *

What are the characteristic features of disorders of primary hemostasis?

*symptoms of mucosal bleeding* *epistaxis *hemoptysis *GI bleeding *hematuria *menorrhagia *Intracranial bleeding occurs with severe thrombocytopenia *symptoms of skin bleeding* *petechiae *purpura *ecchymoses *easy bruising *Petechiae are a sign of thrombocytopenia and are not usually seen with qualitative disorders*

What are the dual hemostatic defects seen in von Willebrand Disease?

1) Deficiency of vWF leads to a *failure of platelet adhesion*,resulting in deficient platelet plug formation manifestation clinically by primary hemostatic bleeding and prolonged bleeding time 2) *A functional deficiency of factor VIII* occurs as a consequence of the deficit of vWF, its carrier protein. Deficiency is manifest by secondary hemostatic bleeding and *prolonged PTT*

Steps in primary hemostasis

1) Transient vasoconstriction - mediated by neural reflex & endothelin release by damaged endothelial cells 2) Vessel injury exposes subendothelial collagen 3) vWF binds exposed subendothelial collagen. Platelets bind vWF using *GP1b* receptor 4) Platelet degranulation - Adhesion induces shape change in platelets; Degranulation => Release of multiple mediators ADP (promotes GP2b/3a receptor expression on platelets) and TXA2 (promotes platelet aggregation) 5) Platelet aggregation - GP2b/3a aggregates platelets using circulating fibrinogen as a linker

Steps in Secondary hemostasis

1. Coagulation cascade generates thrombin 2. Thrombin converts fibrinogen in the platelet plug to fibrin 3. Fibrin is then cross-linked, yielding a stable platelet-fibrin thrombus

Dr. Sattar's way of organizing the Coagulation Cascade

12,11,skip 10, 9, 8 Intrinsic is on the left left has more letters so it is useful to measure PTT Factor 12 is activated by subendothelial collagen or SEC Heparin is commonly referred to as HEP and is therefore on the left *PTT,SEC,HEP all have three letters Common Pathway: 10,5,2,1 1*2*5=10 Extrinsic is on the right 7 Extrinsic is just like my ex, all by herself (7) How do we remember that intrinsic is on the left? INtrinsic is on the same side as heparIN HEP is on the LEPt

What is the normal platelet count?

150,000-400,000/µL mean platelet counts in pregnant women generally are lower

A 27-year-old male presents to the emergency department with a one day history of progressive confusion and oliguria. The patient has had several episodes of epistaxis and bleeding gums since the onset of his illness. Past medical history is unremarkable and the patient does not take medications. Temperature is 39C, blood pressure is 100/62 mm Hg, pulse is 95/min, and respiratory rate is 18/min. Physical exam is notable for a purpuric rash in the lower extremities bilaterally. Peripheral blood smear is shown in Figure A. Which of the following is the most likely mechanism behind the patient's illness? FIGURES: A 1. Defect in platelet aggregation 2. Deficiency in degradation of von Willenbrand Factor (vWF) multimers 3. Peripheral platelet destruction 4. Defect in platelet-to-collagen adhesion 5. Decreased levels of von Willenbrand Factor (vWF)

2. Deficiency in degradation of von Willenbrand Factor (vWF) multimers The patient presents with signs and symptoms of thrombotic thrombocytopenic purpura (TTP). The vWF metalloprotease ADAMTS13 is deficient in TTP, leading to decreased degradation of vWF multimers and subsequent clotting disorders due to a deficiency of available vWF. Patients presenting with thrombocytopenia and microangiopathic hemolytic anemia should be admitted to the hospital with a presumptive diagnosis of TTP. Signs and symptoms include fever, neurological symptoms and mental status changes, renal impairment, and thrombocytopenia. Labs may also show prolonged bleeding time and evidence of hemolytic anemia such as elevated bilirubin and LDH.

A 15-month-old boy is brought to his pediatrician by his mother with a swollen and painful right elbow. She reports that he stumbled and fell on the carpeted floor of their living room, hitting his right elbow on the ground. The mother reports that he did not appear to be in a great deal of pain after the fall, and that she noted the swelling of the joint a few hours after the fall. He recently started walking approximately 2 weeks ago. He does not have any known medical issues, and he is not currently on medication. The mother's pregnancy was without complications and the boy was delivered vaginally without complications at 40 weeks. Aspiration of the right elbow joint reveals frank blood. Which of the following should be included in the work-up of this patient? 1. Peripheral blood smear 2. Creatinine level and percutaneous kidney biopsy 3. Prothrombin time/partial thromboplastin time 4. 24 hour urine collection for porphyrin levels 5. Rheumatoid factor

3. Prothrombin time/partial thromboplastin time This pediatric patient is presenting with hemarthrosis following relatively minor trauma. Platelet count and coagulation studies, including CBC (for platelet count), PT/INR, and PTT, should be obtained to rule out an underlying coagulopathy. There are numerous causes of hemarthrosis, including: trauma, bleeding disorders (hemophilia), neurologic deficits, arthritis, neoplasms, vascular damage, and recent joint arthroplasty. Pharmacologic anticoagulation may also predispose a patient to develop hemarthrosis; this is most commonly seen in patients with supratherapeutic levels of warfarin.

A 45-year-old man is brought to the emergency room by his wife because he has been acting confused for the past day. He is febrile, with an oral temperature of 103.6 deg F; vital signs are otherwise stable. His physical exam is significant for the finding shown in Figure A; he has never noticed lesions like these before. He also has subtle right-sided weakness affecting upper and lower extremities. Labs reveal: hemoglobin 7.0 g/dL, hematocrit 21%, white blood count of 10.2 x 10^3 µL, and platelet count of 20 x 10^3 per µL. PT/INR and PTT are normal. A peripheral blood smear is shown in Figure B. What is the most likely diagnosis? 1. Idiopathic thrombocytopenic purpura 2. Disseminated intravascular coagulation 3. Thrombotic thrombocytopenic purpura 4. Hemolytic uremic syndrome 5. Evan's syndrome

3. Thrombotic thrombocytopenic purpura This clinical presentation is consistent with thrombotic thrombocytopenic purpura (TTP), which is associated with a pentad of signs and symptoms including fever, microangiopathic hemolytic anemia, thrombocytopenia (with associated petechiae), renal dysfunction, and neurological or mental status changes. TTP is a rare and severe bleeding disorder caused by strands of fibrin being deposited in multiple small vessels and the presence of hyaline thrombi affecting multiple organs, including the kidneys and brain. It presents with the pentad of symptoms described above. Pertinent laboratory findings include: anemia, thrombocytopenia (with prolonged bleeding time), elevated indirect bilirubin and LDH, negative Coombs' test, and normal PT/INR and PTT. In TTP there is reduced ADAMTS13 activity. This metalloprotease is involved in the cleaving of von Willebrand factor (vWF); when its activity is reduced, unusually large vWF multimers accumulate and cause aggregation and activation of platelets and subsequent thrombi.

A 37-year-old woman presents to the emergency department complaining of generalized malaise, weakness, headache, nausea, vomiting, and diarrhea; she last felt well roughly two days ago. She is otherwise healthy, and takes no medications. Her vital signs are: T 38.0, HR 96 beats per minute, BP 110/73, and O2 sat 96% on room air. Examination reveals a somewhat ill-appearing woman; she is drowsy but arousable and has no focal neurological deficits. Initial laboratory studies are notable for hematocrit 26%, platelets of 80,000/mL, and serum creatinine of 1.04 mg/dL. Which of the following is the most appropriate treatment at this time? 1. High-dose glucocorticoids 2. Cyclophosphamide and rituximab 3. Vancomycin and cefepime 4. Plasma exchange therapy 5. Urgent laparoscopic splenectomy

4. Plasma exchange therapy This patient presents with symptoms consistent with thrombotic thrombocytopenic purpura (TTP), a condition caused by deficiency in the enzyme ADAMTS13. Initial management is prompt initiation of plasma exchange therapy. TTP is a life-threatening condition; the pathogenesis is due to the deficiency in the enzyme ADAMTS13, a metalloproteinase that normally cleaves von-Willenbrand factor (vWF). Without this cleavage step, vWF remains oversized, leading to over-activation of platelets and thus thrombus formation. Clinically, patients typically present with vague symptoms as in the question stem, and sometimes with neurological symptoms. Laboratory studies demonstrate hemolytic anemia (with schistocytes), thrombocytopenia, and elevated creatinine. TTP is a clinical diagnosis, but it can be confirmed by a depressed ADAMTS13 activity. The mainstay of management is plasma exchange.

You are counseling a pregnant woman who plans to breast-feed exclusively regarding her newborn's nutritional requirements. Which vitamins should be given to the newborn? 1. Folic acid 2. Vitamin B6 3. Vitamin K 4. Vitamin D 5. Vitamin K and Vitamin D

5. Vitamin K and Vitamin D *Human breast milk is low in vitamin D and vitamin K* Newborn infants who are exclusively breast-fed require vitamin D and vitamin K supplementation. Both vitamin K and vitamin D should be given in this case. Quantities in breast milk are inadequate for the newborn. Vitamin K is usually given to all babies, regardless of feeding status, as an injection at the time of birth to prevent hemorrhagic disease of the newborn. Vitamin D is made with exposure to sunlight, but the quantities synthesized may be inadequate especially for darker-skinned neonates. Breast milk does provide sufficient thiamine and folic acid.

A 65-year-old woman on hemodialysis for chronic renal failure requires an urgent dental extraction for an abscessed tooth. Of the following, the most appropriate agent to administer to reduce the risk of significant bleeding would be A) desmopressin B) conjugated estrogen C) erythropoietin D) fresh-frozen plasma E) aminocaproic acid

A is correct Chronic uremia produces a complex abnormality of hemostasis, but patients generally have a prolonged bleeding time due to abnormal platelet function. Desmopressin given before the planned dental extraction is a reasonably safe and rapid way to decrease the risk of bleeding. Both conjugated estrogens and erythropoietin can also reduce the risk of bleeding in patients with uremia undergoing surgical procedures. However, since the effect is delayed, they would not be appropriate in an acute setting. The use of fresh-frozen plasma will not ameliorate prolongation of the bleeding time. The use of the fibrinolysis inhibitor -aminocaproic acid may have some utility in primary mennorhagia, genitourinary tract bleeding after prostate surgery, mild hemophilia, or profound thrombocytopenia or to reduce blood loss after cardiac or joint surgery.

ADAMTS13

ADAMSTS13 is a metalloprotease that normally cleaves vWF multimers into small monomers for eventual degradation

What is the most common acquired antibody against coagulation factor?

Anti-Factor8 Also known as acquired hemophilia, clinical and lab presentations are very similar to congenital hemophilia except there is *no prior history of any bleeding episodes*

How is a the bleeding time affected by a disorder or primary hemostasis?

Bleeding time is increased

Vitamin K Deficiency is most commonly seen in which populations?

Deficiency most commonly seen in *newborns lack gut colonization by bacteria that produce vitamin K newborns are given IM vitamin K shot at birth for prophylaxis *malabsorptive conditions (vit K is a fat soluble vitamin) *long-term antibiotic therapy kills gut bacteria that produce vitamin K *Decrease in hepatic function can decrease vitamin K activation

An 8-year-old girl is brought to the emergency department after experiencing sudden severe dyspnea. On examination, she has upper airway obstruction from soft tissue swelling in her neck. A radiograph shows a hematoma compressing the trachea. Laboratory studies show her prothrombin time is normal, but her partial thromboplastin time is increased. Further testing reveals less than 1% of normal factor VIII level. Both parents and two female siblings are unaffected by this problem, but a male sibling has experienced a similar episode. Which of the following genetic abnormalities is most likely to account for the findings in this girl ? A Autosomal dominant mutation B Autosomal recessive mutation C Genomic imprinting D Germline mosaicism E Random X inactivation F Spontaneous new mutation

E Random X inactivation This girl has features of hemophilia A. This X-linked recessive condition is expected to occur in males, however, who inherit the one maternal X chromosome with the genetic mutation, and they do not have another X chromosome with a normal functional allele, as is the case in her brother. Hemophilia in a female can be explained by the Lyon hypothesis, which states that only one X chromosome in a female is active (the "turned off" X chromosome is the Barr body) for most genes, but this inactivation is a random event. Some individuals are out on the tail end of the Poisson distribution of random events and have few active X chromosomes with the normal allele, leading to markedly diminished factor VIII levels.

A 68 y/o caucasian man is admitted with Dx of left lower lobe pneumonia and is started on gatifloxacin. He has a long hx of diabetes, hypothyroidism, hypercholesterolemia and hypertension.He also has diabetic retinopathy, peripheral neuropathy and nephropathy. He has an AV-fistula placed for a possible dialysis. His medications are insulin, furosemide, atorvastatin, metoprolol and levothyroxine. After having his blood drawn for some lab studies today, he bleeds persistently. Lab: Hb---------------- 11.5 Platelets--------- 160,000 Blood glucose-- 178 BUN------------- 56 Cr--------------- 3.5 Which of the following is the most likely cause of his bleeding? A-DIC B-Factor VIII deficiency C-Consumptive coagulopathy E-Platelet dysfunction F-Thrombocytopenia

E. Platelet Dysfunction (associated with uremia)

Platelets bind vWF using _________ receptor

GP1b

Platelets aggregate to each other using __________ receptor

Gp2b/3a

What is another name for Factor 12?

Hagemann Factor

Which clotting factors are affected by Vitamin K?

II, VII, IX, X, protein C, protein S are the vitamin K-dependent Factors SEVEral TENd TO NIcely Stop Clots

What is the most common cause of thrombocytopenia in children and adults?

ITP (Idiopathic Thrombocytopenic Purpura)

How can you differentiate ITP from TTP

ITP can be distinguished from other hematologic causes of thrombocytopenia via the absence of fever, splenomegaly, schistocytes on blood smear, and an abnormal PT/PTT.

Mechanism of IVIG action in immune thrombocytopenic purpura.

IVIG has no direct activity against platelets. Used acutely to increase platelt count It is administered in order to prevent the action of macrophages against platelets: By stopping up all the FC receptors on the macrophages, IVIG leaves no room for the antibodies on the platelets. Thus it shuts off platelet destruction.

Describe the Lab values seen in Vitamin K deficiency

Increased PT and PTT NORMAL bleeding time

Treatment of Idiopathic Thrombocytopenic Purpura

Initial treatment is corticosteroids Children respond well Adults may show early response but often relapse IVIG used acutely to increase platelet count Splenectomy

Lab Findings in Hemophilia A vs Hemophilia B

Labs show elevated PTT norrmal PT *platelet count* bleeding time reduced factor 8 (Hemophilia A) factor 9 (Hemophilia B)

Describe the pathophysiology of MAHA

Mechanism of MAHA is due to a formation of a fibrin mesh due to increased activation of the system of coagulation. The red blood cells are physically cut by these protein networks,

Bleeding Time Test

Normal bleeding time is between 2-7 minutes

Prothrombin Time (PT) measures the integrity of the _________ (intrinsic/extrinsic) system as well as factors common to both systems and Partial Thromboplastin Time (PTT), measures the integrity of the ___________ (intrinsic/extrinsic) system and the common components.

PT: extrinsic PTT: intrinsic

What is the treatment of TTP and HUS?

Plasmaphareresis and Corticosteroids (particularly in TTP) Corticosteroids may decrease the production of autoantibodies

While disorders of primary hemostasis are usually due to abnormalities in ________, disorders of secondary hemostasis are usually due to abnormalities in ________

Primary: Platelets Secondary: Factors of the Coagulation Cascade

Factors of the coagulation cascade are produced by the _______ in an inactive state. What are the requirements of activation?

Produced by the liver Requires exposure to an activating substance Phospholipid surface (surface of the platelets) Calcium

Are petechiae a sign of quantitative or qualitative plate disorders?

Quantitative Petechiae are a sign of thrombocytopenia and are not usually seen with qualitative disorders

Ristocetin Test

Ristocetin is an antibiotic that causes von Willebrand factor to bind the platelet receptor glycoprotein Ib (GpIb), so when ristocetin is added to normal blood, it causes agglutination. In von Willebrand disease, where von Willebrand factor is absent or defective, abnormal agglutination occurs

What activates Factor 12?

Subendothelial Collagen/damaged blood vessel walls (according to Pathoma) Factor 12 is activated by negatively charged substances according to wiki

What is the role of TXA2? What is the role of ADP? What is the role of fibrinogen? (in primary hemostasis)

TXA2: ADP: Fibrinogen:

Muscle Hematomas characteristic of Hemophilia occur most commonly in which muscles?

The Calf and Psoas Muscle

What is the goal of secondary hemostasis?

The goal of secondary hemostasis is to convert fibrinogen into fibrin to stabilize the loose platelet plug formed in primary hemostasis.

What is the purpose of primary hemostasis? What is the purpose of secondary hemostasis?

The purpose of primary hemostasis is *formation of a weak platelet plug* that serves to prevent or lessen the extent of hemorrhage. The goal of secondary hemostasis is to convert *fibrinogen into fibrin to stabilize the loose platelet plug* formed in primary hemostasis.

Mechanism of Splenectomy in immune thrombocytopenic purpura.

The spleen is both the site of synthesis of the antiplatelet antibodies seen in ITP as well as the site of destruction of antibody-coated platelets Two birds killed with one stone Splenectomy is used in refractory cases

What is the end product of the coagulation cascasde?

Thrombin

__________ converts Fibrinogen to Fibrin

Thrombin

What activates Factor 7?

Tissue Thromboplastin/ Tissue Factor

What is the common treatment for von Willebrand Disease? Describe the mechanism.

Treatment generally consists of desmopressin (ddAVP) which causes *release of vWF from Weibel-Palade bodies within endothelial cells.* *Desmopressin is contraindicated in certain subtypes of von Willebrand disease (i.e. type 2B).*

How does uremia impair platelet function?

Uremia disrupts both platelet adhesion and aggregation Seen primarily in dialysis patients Platelet count will be normal as this is a qualitative and not quantitative disorder Primarily manifests as GI bleeding Dialysis may improve symptoms

What is the first step in primary hemostasis?

Vasoconstriction is the initial response to vessel injury. It is mediated primarily by endothelin (ET-1), an extremely potent vasoconstrictor peptide synthesized by injured endothelium. Also mediated by reflex neural stimulation

An infant whose mother was taking anticonvulsant therapy during pregnancy is at risk for which vitamin deficiency?

Vitamin K

What is the most common inherited coagulation disorder?

Von Willebrand Disease

What are the three major differences between the clinical presentation of von Willebrand disease and the hemophilias (inheritance, type of hemorrhage, bleeding time)?

Von Willebrand disease can be distinguished from the hemophilias in three major ways: *Autosomal dominant inheritance pattern* (hemophilias are autosomal or X-linked recessive) *Bleeding primarily from mucous membranes*(hemarthrosis is seen in severe cases of hemophilia) *Bleeding time is prolonged* (in hemophilia, there is a normal bleeding time)

Where does von willebrand factor come from?

Weibel-Palade Bodies of endothelial cells Alpha granules of Platelets * ** fix this one

30 year old G1P0 reports to your office for OB visit at 15 weeks gestational. Labs drawn 4 weeks ago have platelet count of 60,000. Labs within normal limits. BP is 120/80. Her urine dips shows trace protein. Meds: vitamin. PMH: bleeding in gums, easy bruising. Diagnosis? a. autoimmune thrombocytopenia b. gestational thrombocytopenia c. ITP d. HELLP syndrome e. Pregnancy induce hypertension

a) ITP occurs in the twenties or thirties and is more common in women than in men. Diagnosis of ITP is one of exclusion. There are no pathognomonic signs, symptoms, tests. ITP usu. has less than 100,000 w/o splenomegaly. Women have a history of easy bruising and nose and gum bleeds that precede pregnancy. If platlet counts are maintained above 20K, hemorrhagic episodes do not usually occur. If IgG antibodies destroy platelet consumption in the spleen, then transfusion may be necessary. Platelet counts return to normal in about 3 months. Listen, HELLP syndrome is assoc. w/ thrombocytopenia, but this occurs in the 3rd trimester and is assoc. w/ hypertension. In neonatal alloimmune thrombocytopenia, there is a maternal alloimmunization to fetal platelet antigens. Mother is healthy and has a normal platelet count, but makes antibodies that cross the placenta and destroy fetal neonatal platlets.

Disorders of primary hemostasis are usually due to abnormalities in _______ They can be divided into _________ or ___________ disorders

usually due to abnormalities in *platelets* divided into *quantitative* or *qualitative*

All of the clotting factors are synthesized in the liver except?

vWF