W11- Lecture 58- Blood 2

Question 1

what compound causes haemopoietic stem cells to differentiate into megakaryoblasts, which produce megakarocytes ?

Answer 1

Thrombopoietin

Question 2

what is the effect of Thrombopoietin on haemopoietic stem cells?

Answer 2

causes haemopoietic stem cells to differentiate into megakaryoblasts

Question 3

what are platelets ? quantity/ml life span 5-9 days

Answer 3

Small anucleate cells required for haemostasis 150000 – 400000/ml Life span 5-9 days

Question 4

describe the steps in Haemostasis that happen upon injury

Answer 4

Vascular spasm: arteries/ arterioles constrict to reduce blood flow Platelet plug formation(thrombus formation) Blood clotting(strengthened by fibrin )

Question 5

name three extracellular matrix proteins that are required for Platelet plug formation

Answer 5

vWF Fibrinogen Collagen

Question 6

what are the steps in Platelet plug formation

Answer 6

Adhesion Outside-in signalling- integrin activation Secretion Aggregation Thrombin production

Question 7

how does aspirin act on platelets to prevent clots ?

Answer 7

Aspirin acts on TXA2 alpha – stops production of this which prevents influence of ADP – which changes the shape of the platelet

Question 8

abnormality of what gene produces this disorder ? Bernard-Soulier Glanzmann thrombasthenia symptoms

Answer 8

Bernard-Soulier : abnormality in the genes for glycoprotein Ib/V/IX. Glanzmann thrombasthenia : abnormality in the genes for glycoproteins IIb/IIIa. Symptoms: Easy bruising Nose bleeds Bleeding from gums Heavy or prolonged menstrual bleeding (menorrhagia) or bleeding after childbirth Abnormal bleeding after surgery, or dental work Rarely, vomiting blood or passing blood in stool due to bleeding from the gut (gastrointestinal hemorrhage)

Question 9

what is a Storage pool deficiencies in terms of platelets ?

Answer 9

Some are caused by a lack of granules, most common ones are caused by a failure of the platelets to empty the granules

Question 10

what isDelta storage pool deficiency? linked to any other conditions ?

Answer 10

a lack of dense granules. Can be a feature of other inherited conditions (such as Hermansky-Pudlak syndrome and Chediak-Higashi syndrome).

Question 11

what is grey platelet syndrome ? impact

Answer 11

Grey platelet syndrome is a very rare platelet disorder caused by a lack of alpha granules and the chemicals normally stored inside them. Without these proteins, platelets can not stick to the blood vessel wall, clump together the way they should, or repair the injured blood vessel.

Question 12

what is the difference between extrinsic and intrinsic blood clotting which is faster ? which is initiated by TF

Answer 12

Extrinsic has fewer steps and is rapid. Is initiated by TF leaking into the blood from cells outside the blood stream Intrinsic is more complex and is slower. Outside tissue damage is not needed e.g. caused by endothelial cell damage

Question 13

describe the intrinsic coagulation

Answer 13

Intrinsic is more complex and is slower. Outside tissue damage is not needed e.g. caused by endothelial cell damage 1.Surface contact activates FXII 2.FXIIa activates FXI and releases bradykinin (a vasodilator) from HMWK 3.Ca2+ & FXIa activate FIX, a serine protease 4.FIXa hydrolyses FX (along with Ca2+, and phosphatidylserine on activated platelets, and FVIIIa- the tenase complex) 5.FVIII is a co factor activated by thrombin from platelets 6.FX is activated leading to the common pathway

Question 14

describe extrinsic coagulation

Answer 14

Extrinsic has fewer steps and is rapid. Is initiated by TF leaking into the blood from cells outside the blood stream 1.FVII is activated by thrombin and FXa (from the intrinsic pathway) 2.FVIIa and its cofactor TF (FIII) activate FX

Question 15

describe the common pathway for coagulation

Answer 15

Common pathway 1.FXa cleaves prothrombin (FII) on the surface of activated platelets (creates a prothrombinase complex with Ca2+ , phospholipids, prothrombin, FXa and FVa) 2.FV is activated by small amounts of thrombin 3.Fibrinogen is converted to fibrin by thrombin 4.Thrombin also activates FXIII which cross-links the fibrin clot

Question 16

describe fibrin action for clots

Answer 16

The clot plugs the ruptured area Clot retraction is the tightening of the fibrin clot The fibrin threads attached to the damaged surfaces of the blood vessel contract as platelets pull on them This pulls the edges of the wound together

Question 17

describe fibrinolysis action in clots

Answer 17

Fibrinolysis dissolves small inappropriate clots and dissolved clots as sites of repair Inactive plasminogen is incorporated into the clot Is activated to plasmin by substances in the body tissue (thrombin and t-PA) Plasmin digests fibrin threads and inactivates fibrinogen, prothrombin and FV and FXII

Question 18

describe Haemophilia A effects is it linked to a chromosome ? extrinsic / intrinsic pathways impact how many ppeople does it effcts (gendered ?) 1: ?

Answer 18

Haemophilia A (X linked leading to FVIII deficiency) Extrinsic pathway (assessed by prothrombin time (ProThrombin time) by addition of TF to plasma) is fine Intrinsic pathway does not work (assessed by activated partial thromboplastin time- Activated Partial Thromboplastin Time)- phospholipids are added to mimic contact factor Affects 1:5000 males

Question 19

describe Haemophilia B is it linked to a chromosome ? how many men does it effect 1:?

Answer 19

Christmas disease, X linked disorder leading to FIX deficiency) Has a normal ProThrombin time but activated Partial Thromboplastin time. Affects 1:30 000 males

Question 20

describe the Haemolytic disease of the new born - transplants -birth

Answer 20

Don’t normally have Rh antibodies Can develop them after blood transfusion, causes problem for later transfusions rhesus neg & rhesus positive conceive a child foetus is rh+ mother ph- cells from ph+ foetus enter mothers blood (at child birth ) sensitisation of antibodies to fight rh + cells in next pregnancy maternal antibodies attach foetal red blood cells

Question 21

how do these compounds prevent clotting ? warfarin EDTA aspirin streptokinase

Answer 21

Warfarin: vitamin K antagonist to prevent clotting factor activation EDTA: to chelate calcium in donated blood Aspirin: inhibits TxA2 synthesis Streptokinase: activates t-PA

Question 22

describe the effects of anaemia effect of anaemia that caused the problems

Answer 22

Reduced oxygen carrying capacity Iron- deficiency Megaloblastic (Large RBC) Pernicious (lack of haemopoiesis) Haemorrhagic Heamolytic Thalassemias (haemoglobin problems)

Question 23

is sickle cell recessive or dominant? any evolutionary advantages ?

Answer 23

recessive Low potassium kills malaria

Question 24

is Haemophilia sex linked ?

Answer 24

x linked and recessive

Question 25

what are Leukaemias? Why can leukaemia cause bleeding problems and anaemia?

Answer 25

production of malignant WBC cells, supress production of all normal cells in RBM less platelets in the blood plasma to clot

Question 26

what are the onset + age of these leukemias ? Acute lymphoblastic leukaemia Acute myelogenous leukaemia Chronic lymphoblastic leukaemia Chronic lymphoblastic leukaemia causes

Answer 26

Acute lymphoblastic leukaemia: short onset, derived from lymphoid stem cells. Most common in children Acute myelogenous leukaemia. Affects all ages Chronic lymphoblastic leukaemia. Most common in adults (55+) Chronic myelogenous leukaemia: prolonged onset, derived from myeloid stem cells. Mostly in adults Causes often unknown but can be radiation or chemotherapy, genetics (down syndrome), environmental factors, viral e.g. Epstein-Barr virus

Question 27

what is a Bone Marrow Transplant issues

Answer 27

Replacement of cancerous or abnormal red bone marrow with healthy RBM Patient RBM is destroyed by chemotherapy and whole body radiation Healthy RBM can be from a donor or patient if in remission Marrow migrates to red bone marrow cavities and multiplies Can create graft vs. host disease