Hello again, Rosehi,
If you can wade through a jargon-filled professional document from www.nhlbi.nih.gov, then search for “von willebrands blood test evaluation” using Google and click on the nhlbi.nih.gov choices. Your answers are under the sub-section called “Initial Tests for VWD” which is about the third page of the document after the “decision tree” pages.
In general, the body’s coagulation scheme has several pathways. Failure of any of the pathways leads to bleeding problems. Hyperactivity of any of the pathways leads to clots where you don’t want them so you can see that coagulation disorders are inherently complex and are very dependent on the “balance” between bleeding and coagulation. Hemophilia A is a lack of Factor VIII due to a genetic disorder or the immune system mistakenly destroying Factor VIII or the vonWillebrands factor, a large protein which clumps around Factor VIII in the blood stream and protects it from the immune system. Factor VIII is a key molecule used in the series of steps that form a clot. It is necessary for the formation of the fibers that hold the clot together.
VWD is caused by a lack of vonWillebrands protein or a malformation of the clumps of VWF that protect the Factor VIII. The body stores VWF in little sacks located in the tissue that makes up blood veins (endothelial tissue). (granulocytes are the little sacks) . If you cut yourself, you cut capillary and/or other endothelial tissue and this releases VWF at the site of the cut, IF YOU HAVE ANY. The VWF clumps permit the FVIII to help form the clot at the wound site.
The PT blood test looks for Factor IX (nine), the lack of F IX causes Hemophilia B. The PTT or APTT tests for the activity of F VIII (eight). The INR test compares the amount of Factor IX and Factor VIII. The PT and the PTT are reported, usually, as a time, clotting time. The reference ranges used vary from place to place but a PTT much over 26 seconds is showing some lack of coagulation in the F VIII coagulation path. Something is preventing F VIII from doing its job. Since INR is a ratio calculated from PT and PTT, it will deviate if one or the other is unusual.
VWF:Ag tests for the amount of VWF in the blood. It will not show abnormal VWF, just what the VWF concentration is. It does not test for F VIII even though F VIII is associated with VWF.
VWF:RCo tests for the ability of VWF to interact with other blood chemicals that help produce a structure of needed blood particles that are then removed from the blood by other body processes causing a lack of VWF and other blood platelets in blood. The VWF can be disturbed by, for instance, clapping heart valves and turbulence in the blood stream that physically alters the VWF size and shape. One reason that P-humate or Alphanate F III, VWF IV treatments should be given slowly with a larger IV needle is precisely to limit turbulence at the tip of the IV needle. I always tell the technician to take longer than necessary and to do the timing with a watch, not just guess, as the plunger on the push IV is depressed. I am INSISTENT on this approach! I don’t want those large multimeres of VWF to break apart as they go into the blood stream.
The Factor VIII assay measures the effectiveness of F VIII actually in the blood stream. If the VWF tests are in the reference ranges and the F VIII is near zero, then Hemophilia A is a possibility. If the F VIII is less than optimal but non-zero then something is going on with VWF. Since VWF protects the F VIII and is a large “multimeric” molecule, ie. to work, a VWF molecule has to attach to other VWF molecules to form a kind of capsule that surrounds the F VIII molecule- a multimere- there are a number of failure modes, each one of which causes a different form of VWD.
The “Multimere” test or “Blood Smear” tests examines the VWF particles to determine their size. Like Goldilocks and the three bears, the multimere VWF particles can’t be too big or too small, nor can they be the wrong shape. Each of those results is a different form of VWD. Unfortunately, these tests, especially the F VIII test and the multimere test are subject to false results as a consequence of how the sample is treated between blood draw and analysis. Drawing conclusions from one test is a little chancy.
The reference ranges that determine what is normal and what is abnormal should be based on the WHO. World Health Organization, standards. The results labelled IU/mL or IU/dL are just chemical jargon for International Units per milliliter or deciliter and are concentrations. The results can also be reported as percents of normal. The multimere tests in my experience come back as a description of the size of the multimeres or the multimeric distribution. The heart valve clapping breaks the multimeres down and if your multimere test comes back with mostly small multimeres, you probably will have an ultrasound of your heart valve function. I really enjoyed seeing my heart valves open and shut!!
So, RoseHi and everybody else, write your questions for your medical person down on paper and give them a copy. When you are face to face with them and they have a written copy of your questions it is harder for them to rush you out of the office! Be Strong!!!
John the elder